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University of Georgia
1.
Stramiello, Michael.
Pharmacological and electrophysiological characterizations of dopaminergic modulation of long-term potentiation in the hippocampus CA1 region: implications for addiction.
Degree: PhD, Neuroscience, 2010, University of Georgia
URL: http://purl.galileo.usg.edu/uga_etd/stramiello_michael_201005_phd 
► Over the past fifty years, our understanding of dopamine has evolved from a mere acknowledgement of its precursory status in norepinephrine production to the realization…
(more)
▼ Over the past fifty years, our understanding of dopamine has evolved from a mere acknowledgement of its precursory status in norepinephrine production to the realization that it orchestrates complex modulatory activity in the striatum (reviewed by Onn et al., 2000), the prefrontal cortex (reviewed by Seamans and Yang, 2004), and the hippocampus (reviewed by Lisman and Grace, 2005). Importantly, the hallmark of addictive drugs is their ability to augment dopamine levels in the brain. Because addiction engages the neurophysiological underpinnings of learning and memory, I focused my research on dopaminergic modulation of synaptic plasticity within the hippocampus CA1 region, the brain’s gateway for storage and recall of many types of information. Specifically, I investigated the ability of dopamine to modulate long-term potentiation (LTP), a persisting enhancement of communication between neurons that serves as a cellular model for learning and memory.
Using extracellular recording methods, I demonstrated that both D1/5 and D3 agonists enhance LTP via distinct pathways that ultimately converge upon NR2B-NMDARs. I also showed that D4 receptor activation inhibits D1/5-mediated, but not D3-mediated, enhancement of LTP. With whole-cell voltage clamp recording technique, I provided evidence that D3-mediated disinhibition in the stratum radiatum of hippocampus CA1 takes place at extrasynaptic GABAA receptors innvervated by µ-opioid receptor-expressing interneurons. Finally, I addressed the laminar-specificity of
cocaine-mediated LTP enhancement in the CA1 region: D3 receptor activation is required for this effect in stratum radiatum; D1/5 receptor activation is required for this effect in stratum oriens. Taken together, my results illustrate the multifaceted nature of dopaminergic modulation of hippocampal LTP and provide numerous pharmacological targets for altering hippocampal output.
Advisors/Committee Members: John Wagner.
Subjects/Keywords: cocaine
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APA (6th Edition):
Stramiello, M. (2010). Pharmacological and electrophysiological characterizations of dopaminergic modulation of long-term potentiation in the hippocampus CA1 region: implications for addiction. (Doctoral Dissertation). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/stramiello_michael_201005_phd
Chicago Manual of Style (16th Edition):
Stramiello, Michael. “Pharmacological and electrophysiological characterizations of dopaminergic modulation of long-term potentiation in the hippocampus CA1 region: implications for addiction.” 2010. Doctoral Dissertation, University of Georgia. Accessed January 24, 2020.
http://purl.galileo.usg.edu/uga_etd/stramiello_michael_201005_phd.
MLA Handbook (7th Edition):
Stramiello, Michael. “Pharmacological and electrophysiological characterizations of dopaminergic modulation of long-term potentiation in the hippocampus CA1 region: implications for addiction.” 2010. Web. 24 Jan 2020.
Vancouver:
Stramiello M. Pharmacological and electrophysiological characterizations of dopaminergic modulation of long-term potentiation in the hippocampus CA1 region: implications for addiction. [Internet] [Doctoral dissertation]. University of Georgia; 2010. [cited 2020 Jan 24].
Available from: http://purl.galileo.usg.edu/uga_etd/stramiello_michael_201005_phd.
Council of Science Editors:
Stramiello M. Pharmacological and electrophysiological characterizations of dopaminergic modulation of long-term potentiation in the hippocampus CA1 region: implications for addiction. [Doctoral Dissertation]. University of Georgia; 2010. Available from: http://purl.galileo.usg.edu/uga_etd/stramiello_michael_201005_phd
2.
Kromrey, Sarah Allyson.
Endogenous hormonal milieu of female cynomolgus monkeys: interaction with cognitive performance, social rank and acquisition of cocaine self-administration.
Degree: 2015, Wake Forest University
URL: http://hdl.handle.net/10339/57103
► There are currently no FDA-approved drug treatments for cocaine abuse. The use of female subjects and a better understanding of the influence of hormones and…
(more)
▼ There are currently no FDA-approved drug treatments for cocaine abuse. The use of female subjects and a better understanding of the influence of hormones and cognitive function may provide valuable information to aid in pharmacotherapy development. The present studies utilized female monkeys housed in groups of four to examine the interactions of social rank and hormone concentrations on vulnerability to cocaine reinforcement and cognitive function. The overarching goal was to characterize how estradiol (E2) and progesterone (P4) concentrations influence cognitive performance, eventual social rank and vulnerability to cocaine self-administration (SA). We also examined how social rank altered these and additional hormonal measures.
Subjects/Keywords: cocaine
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APA (6th Edition):
Kromrey, S. A. (2015). Endogenous hormonal milieu of female cynomolgus monkeys: interaction with cognitive performance, social rank and acquisition of cocaine self-administration. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/57103
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kromrey, Sarah Allyson. “Endogenous hormonal milieu of female cynomolgus monkeys: interaction with cognitive performance, social rank and acquisition of cocaine self-administration.” 2015. Thesis, Wake Forest University. Accessed January 24, 2020.
http://hdl.handle.net/10339/57103.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kromrey, Sarah Allyson. “Endogenous hormonal milieu of female cynomolgus monkeys: interaction with cognitive performance, social rank and acquisition of cocaine self-administration.” 2015. Web. 24 Jan 2020.
Vancouver:
Kromrey SA. Endogenous hormonal milieu of female cynomolgus monkeys: interaction with cognitive performance, social rank and acquisition of cocaine self-administration. [Internet] [Thesis]. Wake Forest University; 2015. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/10339/57103.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kromrey SA. Endogenous hormonal milieu of female cynomolgus monkeys: interaction with cognitive performance, social rank and acquisition of cocaine self-administration. [Thesis]. Wake Forest University; 2015. Available from: http://hdl.handle.net/10339/57103
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Utah
3.
Riedy, Matthew D.
Reinstatement of Cocaine-Seeking Behavior Induced by Discrete Sensory Cues and the Associated Immediate Early Gene Expression.
Degree: PhD, Neurosurgery;, 2010, University of Utah
URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/442/rec/969
► Drug addiction is a serious problem for modern societies worldwide. There are remarkable costs associated with this problem, from the direct costs of the substance…
(more)
▼ Drug addiction is a serious problem for modern societies worldwide. There are remarkable costs associated with this problem, from the direct costs of the substance abuse treatment and prevention healthcare infrastructure to the less direct implications for the criminal justice system and social welfare programs. For individuals there is a loss of health, livelihood, interpersonal relationships, freedom, and ultimately life. The hallmark behavioral feature of addiction is a pattern of intermittent relapse lasting for decades after initial substance abuse. The research community has made a substantial investment of time and resources to better understand the etiology and fundamental features underlying addiction and relapse. Modern theories posit that addiction involves a recurring compulsion by an individual to engage in drug-seeking and drug-taking behaviors despite significant negative consequences. In humans, exposure to drug-associated stimuli and environmental contexts is known to induce an intense state of craving, independent of the length of time since acute drug exposure. Furthermore, neuroimaging studies of humans have suggested that basal ganglia structures may be involved in craving. Progress in the study of basal ganglia-mediated learning and memory has begun to outline a neuroanatomical substrate for the transition of egocentric, selfinitiated goal-directed behavior, to allocentric or externally driven behavior arising from exposure to environmental contexts or particular stimuli. While many elegant experiments have addressed the ability of drug-associated environmental contexts to affect behavior, the ability of discrete drug-associated sensory cues to affect behavior has been less thoroughly addressed. Discrete cues can become associated with drug use by two major operant learning mechanisms that vary in their temporal relationship to the subjective perception of primary reinforcement. The experiments described in this dissertation were designed to identify the extent to which discriminative stimuli and conditioned reinforcers activate the same or different populations of neurons in the dorsal striatum, the main input nucleus of the mammalian basal ganglia. This work has examined, in a novel experimental model of relapse, the capability of discrete sensory cues to elicit reinstatement of drug-seeking behavior and the expression of learning and memory related genes associated with this behavior.
Subjects/Keywords: Cocaine Abuse
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APA ·
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APA (6th Edition):
Riedy, M. D. (2010). Reinstatement of Cocaine-Seeking Behavior Induced by Discrete Sensory Cues and the Associated Immediate Early Gene Expression. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/442/rec/969
Chicago Manual of Style (16th Edition):
Riedy, Matthew D. “Reinstatement of Cocaine-Seeking Behavior Induced by Discrete Sensory Cues and the Associated Immediate Early Gene Expression.” 2010. Doctoral Dissertation, University of Utah. Accessed January 24, 2020.
http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/442/rec/969.
MLA Handbook (7th Edition):
Riedy, Matthew D. “Reinstatement of Cocaine-Seeking Behavior Induced by Discrete Sensory Cues and the Associated Immediate Early Gene Expression.” 2010. Web. 24 Jan 2020.
Vancouver:
Riedy MD. Reinstatement of Cocaine-Seeking Behavior Induced by Discrete Sensory Cues and the Associated Immediate Early Gene Expression. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2020 Jan 24].
Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/442/rec/969.
Council of Science Editors:
Riedy MD. Reinstatement of Cocaine-Seeking Behavior Induced by Discrete Sensory Cues and the Associated Immediate Early Gene Expression. [Doctoral Dissertation]. University of Utah; 2010. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/442/rec/969
4.
Hamilton, Lindsey Rebecca.
Neurobiological and Behavioral Phenotypes and Cocaine Self-Administration in Adult Rhesus Monkeys Exposed to Cocaine Throughout Gestation.
Degree: 2010, Wake Forest University
URL: http://hdl.handle.net/10339/30400
Maternal cocaine addiction is a significant public health problem yet
Subjects/Keywords: Cocaine
…Figure
2. A) Yawning
Elicited
by
Quinpirole
in
Female
Prenatally
Cocaine
Exposed
and… …Control
Monkeys
B) Yawning
Elicited
by
Quinpirole
in
Male
Prenatally
Cocaine
Exposed
and… …Peak
Yawns
Elicited
by
Quinpirole
and
Maximal
Daily
Dose
of
In
Utero
Cocaine
107… …Effects
of
SKF
81297
on
Eye‐Blinking
Rates
in
Prenatally
Cocaine
Exposed
Monkeys
C) Group… …Delay
Value
Percentage
Choice
for
the
Delayed
Reinforcer
Curves
for
a
Prenatally
Cocaine…
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APA ·
Chicago ·
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CSE |
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APA (6th Edition):
Hamilton, L. R. (2010). Neurobiological and Behavioral Phenotypes and Cocaine Self-Administration in Adult Rhesus Monkeys Exposed to Cocaine Throughout Gestation. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/30400
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hamilton, Lindsey Rebecca. “Neurobiological and Behavioral Phenotypes and Cocaine Self-Administration in Adult Rhesus Monkeys Exposed to Cocaine Throughout Gestation.” 2010. Thesis, Wake Forest University. Accessed January 24, 2020.
http://hdl.handle.net/10339/30400.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hamilton, Lindsey Rebecca. “Neurobiological and Behavioral Phenotypes and Cocaine Self-Administration in Adult Rhesus Monkeys Exposed to Cocaine Throughout Gestation.” 2010. Web. 24 Jan 2020.
Vancouver:
Hamilton LR. Neurobiological and Behavioral Phenotypes and Cocaine Self-Administration in Adult Rhesus Monkeys Exposed to Cocaine Throughout Gestation. [Internet] [Thesis]. Wake Forest University; 2010. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/10339/30400.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hamilton LR. Neurobiological and Behavioral Phenotypes and Cocaine Self-Administration in Adult Rhesus Monkeys Exposed to Cocaine Throughout Gestation. [Thesis]. Wake Forest University; 2010. Available from: http://hdl.handle.net/10339/30400
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
5.
Pattison, Lindsey Patricia.
Functional Alterations in the Dopamine Transporter of Rodents following Self-Administration of Cocaine, Heroin and Speedball.
Degree: 2013, Wake Forest University
URL: http://hdl.handle.net/10339/38519
► Cocaine/heroin combinations (speedball) induce a synergistic elevation in extracellular dopamine (DA) concentrations ([DA]e) in the nucleus accumbens (NAc) that can explain the continued patterns of…
(more)
▼ Cocaine/heroin combinations (speedball) induce a synergistic elevation in extracellular dopamine (DA) concentrations ([DA]e) in the nucleus accumbens (NAc) that can explain the continued patterns of abuse even after seeking treatment for heroin addiction. To further delineate the mechanism of this neurochemical synergism, in vivo fast-scan cyclic voltammetry (FSCV) was used to compare evoked DA release and DA transporter (DAT)-mediated reuptake kinetic parameters following acute administration of cocaine, heroin and speedball in drug-naïve rats, as well in rats with chronic self-administration (SA) history of cocaine, heroin and speedball. Together, the results have shown that speedball combinations likely induced DA autoreceptor feedback in attempt to regulate increased [DA]e, and that there is also a significant increase in baseline reuptake rate by DAT following chronic speedball SA. In order to deduce the potential mechanism by which DAT is altered to increase reuptake rate, cocaine-like ligands were used in membrane binding assays and quantitative autoradiography for DAT in the NAc of rats to assess the long-term effects of chronic SA of cocaine, heroin and speedball on DAT high- and low-affinity binding sites. The results show a significant increase in affinity of the DAT low-affinity binding site and a shift in DAT binding site composition toward a greater percent of high-affinity binding sites following chronic speedball. These binding data suggest that long-term speedball SA induces a flexibility in the DAT substrate binding sites toward an outward facing conformation in order to increase maximal reuptake rate in compensation for chronically elevated [DA]e. Knowledge of these chronic alterations in DAT function may be able to provide insight into the development of novel pharmacotherapies for the treatment of polysubstance abuse, as well as for cocaine and heroin addictions alone.
Subjects/Keywords: cocaine
…CHAPTER I
Table 1.
Effects of cocaine on the mesolimbic DA system
Table 2.
Compounds used… …combinations
to
elucidate
mechanisms
23
of
cocaine/heroin
40
CHAPTER II
Figure 1… …Representative traces of evoked DA signals detected by FSCV in rat NAc
before and 1 min after cocaine… …cocaine + 0.03 mg/kg heroin, i.v.) injection in
drug-naïve animals (upper panel)… …cocaine (1.0 mg/kg), heroin (0.03
mg/kg) and speedball (1.0 mg/kg…
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Record Details
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APA ·
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MLA ·
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CSE |
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pattison, L. P. (2013). Functional Alterations in the Dopamine Transporter of Rodents following Self-Administration of Cocaine, Heroin and Speedball. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/38519
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Pattison, Lindsey Patricia. “Functional Alterations in the Dopamine Transporter of Rodents following Self-Administration of Cocaine, Heroin and Speedball.” 2013. Thesis, Wake Forest University. Accessed January 24, 2020.
http://hdl.handle.net/10339/38519.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pattison, Lindsey Patricia. “Functional Alterations in the Dopamine Transporter of Rodents following Self-Administration of Cocaine, Heroin and Speedball.” 2013. Web. 24 Jan 2020.
Vancouver:
Pattison LP. Functional Alterations in the Dopamine Transporter of Rodents following Self-Administration of Cocaine, Heroin and Speedball. [Internet] [Thesis]. Wake Forest University; 2013. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/10339/38519.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pattison LP. Functional Alterations in the Dopamine Transporter of Rodents following Self-Administration of Cocaine, Heroin and Speedball. [Thesis]. Wake Forest University; 2013. Available from: http://hdl.handle.net/10339/38519
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
6.
Brutcher, Robert Edwin.
EFFECTS OF SLEEP DISRUPTION AND QUETIAPINE ON COCAINE ABUSE: THE PATH TO DEVELOPMENT OF A MONKEY MODEL OF PTSD.
Degree: 2013, Wake Forest University
URL: http://hdl.handle.net/10339/38531
► The goal of the current research is to systematically evaluate several components needed to develop a monkey model of post-traumatic stress disorder (PTSD). For this…
(more)
▼ The goal of the current research is to systematically evaluate several components needed to develop a monkey model of post-traumatic stress disorder (PTSD). For this dissertation, the aspects of PTSD investigated included sleep disturbance, cognitive disruptions and drug abuse. These studies used Old World macaques, rhesus monkeys, because of their close phylogeny to humans, their similar sleep-wake patterns and their cognitive abilities.
Subjects/Keywords: Cocaine
…LIST OF FIGURES
PAGE
CHAPTER II
Figure 1.
Mean (± SD or SEM) cocaine-choice… …cocaine doses on (A) sleep efficiency, (B) sleep latency,
and (C)… …cocaine baseline (A) and sleep disruption (B) …100
Figure 4.
Mean (… …SEM) sleep measures during baseline cocaine conditions
(light gray bars) and… …p < 0.01; n=7 …101
Figure 4.
Mean (± SEM) percent of cocaine choice for…
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APA (6th Edition):
Brutcher, R. E. (2013). EFFECTS OF SLEEP DISRUPTION AND QUETIAPINE ON COCAINE ABUSE: THE PATH TO DEVELOPMENT OF A MONKEY MODEL OF PTSD. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/38531
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Brutcher, Robert Edwin. “EFFECTS OF SLEEP DISRUPTION AND QUETIAPINE ON COCAINE ABUSE: THE PATH TO DEVELOPMENT OF A MONKEY MODEL OF PTSD.” 2013. Thesis, Wake Forest University. Accessed January 24, 2020.
http://hdl.handle.net/10339/38531.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Brutcher, Robert Edwin. “EFFECTS OF SLEEP DISRUPTION AND QUETIAPINE ON COCAINE ABUSE: THE PATH TO DEVELOPMENT OF A MONKEY MODEL OF PTSD.” 2013. Web. 24 Jan 2020.
Vancouver:
Brutcher RE. EFFECTS OF SLEEP DISRUPTION AND QUETIAPINE ON COCAINE ABUSE: THE PATH TO DEVELOPMENT OF A MONKEY MODEL OF PTSD. [Internet] [Thesis]. Wake Forest University; 2013. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/10339/38531.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Brutcher RE. EFFECTS OF SLEEP DISRUPTION AND QUETIAPINE ON COCAINE ABUSE: THE PATH TO DEVELOPMENT OF A MONKEY MODEL OF PTSD. [Thesis]. Wake Forest University; 2013. Available from: http://hdl.handle.net/10339/38531
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Wake Forest University
7.
Freeman, Willard Morgan.
Functional Neurogenomics of Cocaine.
Degree: 2002, Wake Forest University
URL: http://hdl.handle.net/10339/14669
► Dissertation prepared under the direction of Kent E. Vrana, Ph.D., Associate Professor of Physiology and Pharmacology and Director of Graduate Studies Chronic cocaine abuse causes…
(more)
▼ Dissertation prepared under the direction of
Kent E. Vrana, Ph.D., Associate Professor of Physiology and Pharmacology
and Director of Graduate Studies
Chronic cocaine abuse causes altered neuronal gene expression, morphology, and
physiology. These changes are thought to contribute to an allostatic state of behavior characterized
by compulsive drug seeking, sensitization, tolerance, withdrawal and psychological
dependence. Through the use of cDNA hybridization arrays and immunoreactive
protein quantification, gene expression analysis can be carried out on a functional
neurogenomic scale. This dissertation research identifies changes in gene expression
across three animal models of chronic cocaine administration (non-contigent non-human
primate, non-contingent rat, and self-administering rat), and three brain regions, (nucleus
accumbens, frontal cortex, and hippocampus).
In the non-human primate, chronic cocaine induced the expression of protein tyrosine
kinase 2, mitogen activated protein kinase kinase, â-catenin, and protein kinase A á
catalytic subunit. While each of these genes has important cellular effects, the prime finding
of the study was that they all serve to activate cyclic AMP response element binding
protein or activator protein 1, known mediators of cocaine-responsive gene expression
x
and behavior. In the non-contingent rodent model, hippocampal expression of
protein kinase Cá, protein kinase Cå, metabotropic glutamate receptor 5, potassium
channel Kv1.1, protein tyrosine kinase 2, and â-catenin were induced by cocaine.
Each of these genes could potentially have a number of effects, but, interestingly,
some of the changes observed could act in an antagonistic manner.
In the rat frontal cortex, induction of protein tyrosine kinase 2, activity-regulated cytoskeletal
protein, and a nuclear receptor 77 related antigen were seen with chronic
cocaine administration. In the rat nucleus accumbens, protein tyrosine kinase 2
protein was shown to be significantly up-regulated. Initial hybridization array analysis
of cocaine self-administering rats has produced a number of potentially cocaineresponsive
genes, some of which were observed in the non-contingent rat model.
These studies demonstrate that some changes in gene expression are specific to certain
regions of the brain and others are more ubiquitous. These changes in gene expression
provide hypotheses for future research into the role of functional neurogenomics in physiology
and behavior, and may provide potential targets for pharmacotherapeutic intervention.
Subjects/Keywords: Cocaine
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APA ·
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MLA ·
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CSE |
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Freeman, W. M. (2002). Functional Neurogenomics of Cocaine. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/14669
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Freeman, Willard Morgan. “Functional Neurogenomics of Cocaine.” 2002. Thesis, Wake Forest University. Accessed January 24, 2020.
http://hdl.handle.net/10339/14669.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Freeman, Willard Morgan. “Functional Neurogenomics of Cocaine.” 2002. Web. 24 Jan 2020.
Vancouver:
Freeman WM. Functional Neurogenomics of Cocaine. [Internet] [Thesis]. Wake Forest University; 2002. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/10339/14669.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Freeman WM. Functional Neurogenomics of Cocaine. [Thesis]. Wake Forest University; 2002. Available from: http://hdl.handle.net/10339/14669
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
Boyle, Cody Adam.
Intergenerational Effects Of Embryonic Cocaine Exposure In Zebrafish.
Degree: MS, Biology, 2017, University of North Dakota
URL: https://commons.und.edu/theses/2174
► Cocaine addiction has both genetic and environmentally driven components. Relatively recently several groups have suggested that epigenetic regulation of gene expression might be the…
(more)
▼ Cocaine addiction has both genetic and environmentally driven components. Relatively recently several groups have suggested that epigenetic regulation of gene expression might be the mechanism linking environmental influence and inheritance in drug addiction. We have shown previously that embryonic
cocaine exposure increases physiological and behavioral sensitivity to the drug in longitudinal adults. In this study, we provide evidence that the effects of embryonic pre-exposure to
cocaine are intergenerational in zebrafish. In addition, we show how gene expression in the zebrafish telencephalon, which includes the teleost equivalent of the nucleus accumbens, changes during acute
cocaine treatment during behavioral testing. These experiments outline gene expression pathways not extensively studied in the context of
cocaine response. We show how embryonic exposure to
cocaine affects these gene expression pathways when the longitudinal animals are acutely exposed. Finally, we show how chronic embryonic exposure affects these same pathways in 5-day old embryos.
Advisors/Committee Members: Tristan Darland.
Subjects/Keywords: Cocaine; Intergenerational; Zebrafish
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APA ·
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APA (6th Edition):
Boyle, C. A. (2017). Intergenerational Effects Of Embryonic Cocaine Exposure In Zebrafish. (Masters Thesis). University of North Dakota. Retrieved from https://commons.und.edu/theses/2174
Chicago Manual of Style (16th Edition):
Boyle, Cody Adam. “Intergenerational Effects Of Embryonic Cocaine Exposure In Zebrafish.” 2017. Masters Thesis, University of North Dakota. Accessed January 24, 2020.
https://commons.und.edu/theses/2174.
MLA Handbook (7th Edition):
Boyle, Cody Adam. “Intergenerational Effects Of Embryonic Cocaine Exposure In Zebrafish.” 2017. Web. 24 Jan 2020.
Vancouver:
Boyle CA. Intergenerational Effects Of Embryonic Cocaine Exposure In Zebrafish. [Internet] [Masters thesis]. University of North Dakota; 2017. [cited 2020 Jan 24].
Available from: https://commons.und.edu/theses/2174.
Council of Science Editors:
Boyle CA. Intergenerational Effects Of Embryonic Cocaine Exposure In Zebrafish. [Masters Thesis]. University of North Dakota; 2017. Available from: https://commons.und.edu/theses/2174
Victoria University of Wellington
9.
Morani, Aashish Sultan.
Behavioural Pharmacology of Novel Kappa Opioid Compounds.
Degree: 2011, Victoria University of Wellington
URL: http://hdl.handle.net/10063/4446
► Rationale: Kappa opioid receptor (KOPr) activation by traditional agonists has been shown to produce anti-addiction behaviours. However, adverse effects such as sedation, aversion and depression…
(more)
▼ Rationale: Kappa opioid receptor (KOPr) activation by traditional agonists has been shown to produce anti-addiction behaviours. However, adverse effects such as sedation, aversion and depression have limited their clinical development. Recently, salvinorin A (Sal A), an active component of the plant Salvia divinorum was shown to be a potent and selective KOPr agonist. Sal A has a short duration of effect and quick onset of action. It also produces similar behavioural pharmacology to traditional KOPr agonists. However, little is known about the anti-addiction profile of Sal A. If Sal A and its structural analogues produce anti-addiction properties with fewer adverse effects compared to traditional KOPr agonists, they have potential to be developed into antiaddiction pharmacotherapies. Therefore, Sal A and its structural analogues (DS1, MOM Sal B, EOM Sal B, herkinorin) and Mu opioid receptor (MOPr) antagonist/partial KOPr agonist, nalmefene were tested for their behavioural anti-addiction and adverse effect profiles in rats.
Methods: To test the anti-addiction profile, a within session
cocaine prime induced reinstatement paradigm was used. The selectivity of KOPr agonists in attenuating
cocaine seeking behaviours was tested using sucrose reinforcement (anhedonia) and
cocaine induced hyperactivity in self-administering rats (sedation during reinstatement test). Furthermore, behavioural adverse effects were screened using spontaneous open field activity (motor suppression), conditioned taste aversion (aversion) and forced swim test (depression) in rats. To further quantify the anti-addiction behaviours, the effect of KOPr agonists which attenuated drug seeking selectively without producing motor suppression by themselves were tested for
cocaine produced motor function (hyperactivity and behavioural sensitization) in rats. The effect of serotonin transporter blockade on KOPr agonist induced depressive behaviour was also tested. The effects of KOPr activation on in vitro serotonin transporter function were also determined. Results: Sal A, DS1 and nalmefene attenuated
cocaine prime induced drug-seeking, in a selective manner, via KOPr activation. MOM Sal B, a more potent and long acting Sal A analogue attenuated
cocaine seeking in a non-selective manner. Sal A, DS1 and nalmefene did not induce aversion, however nalmefene suppressed motor function, which was not seen with Sal A and DS1. Furthermore, Sal A and DS1 suppressed
cocaine behavioural sensitization. All three compounds (Sal A, DS1, nalmefene) produced depression. The depressive effects produced by Sal A and DS1 were diminished by blocking the serotonin transporter. Live-cell serotonin transporter assays showed potential differences between traditional (U50488H) and novel (Sal A, DS1) KOPr agonists in their ability to modulate serotonin transporter function. Conclusion: Out of six KOPr compounds tested, Sal A, DS1, MOM Sal B and nalmefene produced anti-addiction behaviours. However, MOM Sal B exposure also suppressed natural reward seeking behaviour. Sal A and DS1…
Advisors/Committee Members: Kivell, Bronwyn, Schenk, Susan.
Subjects/Keywords: Cocaine; Salvinorin; Pharmacology
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APA (6th Edition):
Morani, A. S. (2011). Behavioural Pharmacology of Novel Kappa Opioid Compounds. (Doctoral Dissertation). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/4446
Chicago Manual of Style (16th Edition):
Morani, Aashish Sultan. “Behavioural Pharmacology of Novel Kappa Opioid Compounds.” 2011. Doctoral Dissertation, Victoria University of Wellington. Accessed January 24, 2020.
http://hdl.handle.net/10063/4446.
MLA Handbook (7th Edition):
Morani, Aashish Sultan. “Behavioural Pharmacology of Novel Kappa Opioid Compounds.” 2011. Web. 24 Jan 2020.
Vancouver:
Morani AS. Behavioural Pharmacology of Novel Kappa Opioid Compounds. [Internet] [Doctoral dissertation]. Victoria University of Wellington; 2011. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/10063/4446.
Council of Science Editors:
Morani AS. Behavioural Pharmacology of Novel Kappa Opioid Compounds. [Doctoral Dissertation]. Victoria University of Wellington; 2011. Available from: http://hdl.handle.net/10063/4446
University of Michigan
10.
Brim, Remy Leigh.
Investigations into the Therapeutic Potential of a Bacterial Cocaine Esterase for the Treatment of Cocaine Toxicity and Cocaine Abuse.
Degree: PhD, Pharmacology, 2011, University of Michigan
URL: http://hdl.handle.net/2027.42/84448
► Cocaine use is a widespread problem in the United States with 2 million current users who make about half a million emergency department visits each…
(more)
▼ Cocaine use is a widespread problem in the United States with 2 million current users who make about half a million emergency department visits each year. Although use is prevalent, there is currently no FDA-approved pharmacotherapy to specifically treat
cocaine abuse or
cocaine toxicity. Approaches toward developing therapies for these indications include small molecule inhibitors of
cocaine binding and
cocaine vaccines. These methods have proven to block the strong reinforcing properties of the drug; however, they do not prevent nor reverse cocaine’s serious physiological effects. Our approach to treating
cocaine toxicity and abuse is to rapidly hydrolyze the
cocaine molecule into inactive metabolites using a bacterial
cocaine esterase (CocE), thus eliminating cocaine’s harmful and strong reinforcing effects.
This work has taken major steps toward developing CocE into a viable pharmacotherapy for both
cocaine addiction and toxicity. Initially two thermostabilizing mutations were combined to improve the half-life of CocE. This mutant was pharmacologically characterized in vitro as well as in vivo using rodent models of
cocaine lethality and reinforcement. The pharmacodynamic and pharmacokinetic properties of CocE, including in vivo rates of
cocaine hydrolysis across species, circulating half-life, and mechanisms of elimination, were assessed. CocE’s capacity to hydrolyze
cocaine in the presence of commonly co-abused drugs, and its capacity to hydrolyze active
cocaine metabolites were investigated. The results from these studies support the notion that
cocaine esterase displays strong therapeutic potential, and that it may proceed towards clinical development. Moreover, it is a comprehensive analysis of how protein biologics may be used as effective pharmacotherapeutics.
Advisors/Committee Members: Sunahara, Roger K. (committee member), Woods, James H. (committee member), Gnegy, Margaret E. (committee member), Lukacs, Nicholas W. (committee member), Tesmer, John (committee member).
Subjects/Keywords: Cocaine; Protein-based Theraputic; Cocaine Esterase; Cocaine Abuse; Cocaine Toxicity; Pharmacy and Pharmacology; Health Sciences
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APA (6th Edition):
Brim, R. L. (2011). Investigations into the Therapeutic Potential of a Bacterial Cocaine Esterase for the Treatment of Cocaine Toxicity and Cocaine Abuse. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/84448
Chicago Manual of Style (16th Edition):
Brim, Remy Leigh. “Investigations into the Therapeutic Potential of a Bacterial Cocaine Esterase for the Treatment of Cocaine Toxicity and Cocaine Abuse.” 2011. Doctoral Dissertation, University of Michigan. Accessed January 24, 2020.
http://hdl.handle.net/2027.42/84448.
MLA Handbook (7th Edition):
Brim, Remy Leigh. “Investigations into the Therapeutic Potential of a Bacterial Cocaine Esterase for the Treatment of Cocaine Toxicity and Cocaine Abuse.” 2011. Web. 24 Jan 2020.
Vancouver:
Brim RL. Investigations into the Therapeutic Potential of a Bacterial Cocaine Esterase for the Treatment of Cocaine Toxicity and Cocaine Abuse. [Internet] [Doctoral dissertation]. University of Michigan; 2011. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/2027.42/84448.
Council of Science Editors:
Brim RL. Investigations into the Therapeutic Potential of a Bacterial Cocaine Esterase for the Treatment of Cocaine Toxicity and Cocaine Abuse. [Doctoral Dissertation]. University of Michigan; 2011. Available from: http://hdl.handle.net/2027.42/84448
University of Texas – Austin
11.
Will, Ryan Gregory.
The role of the preoptic area in response to cocaine.
Degree: PhD, Psychology, 2016, University of Texas – Austin
URL: http://hdl.handle.net/2152/39723
► The preoptic area of the hypothalamus is ideally suited to modulate the behavioral and neural response to drugs of abuse such as cocaine. The preoptic…
(more)
▼ The preoptic area of the hypothalamus is ideally suited to modulate the behavioral and neural response to drugs of abuse such as
cocaine. The preoptic area is broken up into two major subregions the medial preoptic area (mPOA) and the lateral preoptic area (LPO), both of which send dense projections to mesolimbic dopamine system. Specifically, both project to the ventral tegmental area (VTA), a brain region implicated in drug-associated reward. Previous work has demonstrated the mPOA is involved in the behavioral and neural response to
cocaine in female rats, however the mechanism through which the mPOA modulates response to
cocaine is unclear. Whether or not the mPOA also plays a role in response to
cocaine in male rats is still not clear. Furthermore the role of the adjacent LPO in response to
cocaine is unexplored, despite its anatomical relationship to the VTA and involvement in intracranial self-stimulation. Here I demonstrate that estradiol acts in the mPOA of female rats to modulate response to
cocaine. Specifically, microinjections of estradiol directly into the mPOA one day prior to
cocaine administration increase
cocaine-induced dopamine levels in the nucleus accumbens. The mPOA is also involved in the behavioral regulation of response to
cocaine in male rats, as mPOA lesions enhanced
cocaine-induced locomotion and reward. Finally, activation of the LPO, with pharmacology or chemogenetics, potentiates reinstatement of
cocaine seeking, an animal model of drug relapse. Together these results demonstrate that the preoptic area as a whole is involved in the regulation of the neural and behavioral response to
cocaine and shed light on underlying regulatory mechanisms.
Advisors/Committee Members: Dominguez, Juan M. (advisor), Marinelli, Michela (advisor), Duvauchelle, Christine L (committee member), Gore, Andrea C (committee member), Jones, Theresa A (committee member), Monfils, Marie H (committee member).
Subjects/Keywords: Preoptic area; Cocaine
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APA (6th Edition):
Will, R. G. (2016). The role of the preoptic area in response to cocaine. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/39723
Chicago Manual of Style (16th Edition):
Will, Ryan Gregory. “The role of the preoptic area in response to cocaine.” 2016. Doctoral Dissertation, University of Texas – Austin. Accessed January 24, 2020.
http://hdl.handle.net/2152/39723.
MLA Handbook (7th Edition):
Will, Ryan Gregory. “The role of the preoptic area in response to cocaine.” 2016. Web. 24 Jan 2020.
Vancouver:
Will RG. The role of the preoptic area in response to cocaine. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2016. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/2152/39723.
Council of Science Editors:
Will RG. The role of the preoptic area in response to cocaine. [Doctoral Dissertation]. University of Texas – Austin; 2016. Available from: http://hdl.handle.net/2152/39723
University of Kentucky
12.
Zheng, Xirong.
Pharmacokinetic and Pharmacodynamic Evaluation of Cocaine Hydrolases for the Treatment of Cocaine Overdose and Cocaine Addiction Using Rodent Models.
Degree: 2019, University of Kentucky
URL: https://uknowledge.uky.edu/pharmacy_etds/102
► Overdose and addiction are two medical complications of cocaine abuse. To date, there is no FDA approved pharmacotherapy specific for cocaine abuse. Cocaine hydrolases (CocHs)…
(more)
▼ Overdose and addiction are two medical complications of cocaine abuse. To date, there is no FDA approved pharmacotherapy specific for cocaine abuse. Cocaine hydrolases (CocHs) have been extensively investigated for its potential in anti-cocaine therapy. Previous studies have demonstrated that CocHs efficiently hydrolyze cocaine to generate biologically inactive metabolites both in vivo and in vitro. However, it has not been studied whether there is gender difference in the therapy using CocHs. In addition, the effectiveness of CocHs is unknown for treating cocaine toxicity when alcohol is co-administered.
The main purpose of this dissertation is to characterize and evaluate efficient CocHs for cocaine overdose and cocaine addiction treatment. In the first set of studies, the effectiveness of human serum albumin-fused CocH1 were studied in male and female rats. The pharmacokinetic profiles, as well as the pharmacodynamic effects of CocH1-HSA were compared in male and female rats. The obtained data clearly demonstrated that CocH1-HSA was equally effective in both genders. The second set of studies investigated the efficiency of Fc-fused CocH5 in reversing cocaine toxicity in rats receiving simultaneous administration of cocaine and alcohol. Results showed that CocH5-Fc rapidly hydrolyzed cocaine and cocaine’s toxic metabolites in rats, and demonstrated that CocH5-Fc was efficient in treating cocaine toxicity when alcohol was simultaneously administered.
In later studies to investigate the effects of CocH5-Fc for the treatment of cocaine addiction, a mathematical model was developed and validated to predict the effects of CocH5-Fc on the disposition of cocaine in rat blood and brain. This model adequately described the effects of CocH5-Fc in accelerating the elimination of cocaine and its toxic metabolites in both rat blood and brain. In conclusion, the studies within the current dissertation demonstrate the clinical potential of CocHs for the treatment of both cocaine overdose and cocaine addiction.
Subjects/Keywords: cocaine overdose; cocaine addiction; cocaine hydrolase; mathematical model; Pharmaceutics and Drug Design
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APA (6th Edition):
Zheng, X. (2019). Pharmacokinetic and Pharmacodynamic Evaluation of Cocaine Hydrolases for the Treatment of Cocaine Overdose and Cocaine Addiction Using Rodent Models. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/pharmacy_etds/102
Chicago Manual of Style (16th Edition):
Zheng, Xirong. “Pharmacokinetic and Pharmacodynamic Evaluation of Cocaine Hydrolases for the Treatment of Cocaine Overdose and Cocaine Addiction Using Rodent Models.” 2019. Doctoral Dissertation, University of Kentucky. Accessed January 24, 2020.
https://uknowledge.uky.edu/pharmacy_etds/102.
MLA Handbook (7th Edition):
Zheng, Xirong. “Pharmacokinetic and Pharmacodynamic Evaluation of Cocaine Hydrolases for the Treatment of Cocaine Overdose and Cocaine Addiction Using Rodent Models.” 2019. Web. 24 Jan 2020.
Vancouver:
Zheng X. Pharmacokinetic and Pharmacodynamic Evaluation of Cocaine Hydrolases for the Treatment of Cocaine Overdose and Cocaine Addiction Using Rodent Models. [Internet] [Doctoral dissertation]. University of Kentucky; 2019. [cited 2020 Jan 24].
Available from: https://uknowledge.uky.edu/pharmacy_etds/102.
Council of Science Editors:
Zheng X. Pharmacokinetic and Pharmacodynamic Evaluation of Cocaine Hydrolases for the Treatment of Cocaine Overdose and Cocaine Addiction Using Rodent Models. [Doctoral Dissertation]. University of Kentucky; 2019. Available from: https://uknowledge.uky.edu/pharmacy_etds/102
13.
Puig, Stéphanie.
Etude intégrée des variations comportementales, neurochimiques et cellulaires de la cocaïne : Analyse des variations à court et à long terme : Importance du profil d’administration et anticipation de l’effet renforçant de la drogue : Integrated study of variations behavioral, neurochemical and cellular of the cocaine.
Degree: Docteur es, Neurosciences, 2012, Université Paris Descartes – Paris V
URL: http://www.theses.fr/2012PA05P620
► La prise répétée de cocaïne entraine la mise en place d’une addiction durable. Cette maladie neuropsychiatrique est un problème de santé public majeur en France…
(more)
▼ La prise répétée de cocaïne entraine la mise en place d’une addiction durable. Cette maladie neuropsychiatrique est un problème de santé public majeur en France et dans le monde. Les effets aigus de la cocaïne sont maintenant bien connus mais il est encore difficile d’établir un consensus des conséquences d’une administration répétée de ce psychostimulant au niveau central. En effet, les résultats rapportés dans la littérature actuelle présentent de nombreuses disparités. Nous pensons que cela pourrait être dû aux différences de protocole d’administration utilisés par chaque laboratoire. Nous émettons l’hypothèse que si à l’heure actuelle il n’existe pas de traitement efficace pour traiter les cocaïnomanes, c’est que les thérapies ne prennent pas en compte les différentes modifications neurobiologiques induites par les différents profils de consommation. Afin de tester cette hypothèse, nous avons comparé deux profils d’administration différents de cocaïne chez le rat. Nous nous sommes intéressés aux conséquences comportementales, neurochimiques et cellulaires après un sevrage court et un sevrage long. Nous avons mis en évidence que les adaptations comportementales (activité locomotrice et exploratoire), neurochimiques (dopamine extracellulaire) et cellulaires (récepteurs dopaminergiques) basales et en réponse à une dose de rappel, sont différentes selon le profil d’administration de cocaïne. Nous avons également mis en évidence une anticipation neurochimique dopaminergique et locomotrice, exactement à l’heure habituelle d’injection et qui varie selon le profil d’administration. Dans un deuxième temps, nous avons montré que le BDNF (Brain Derived Neurotrophic Factor), qui est une neurotrophine du système catécholaminergique, varie à la fois au niveau central et au niveau périphérique, de façon spécifique pour chaque profil d’administration de cocaïne. L’utilisation en clinique de ce biomarqueur périphérique (BDNF), permettrait d’évaluer les variations neurobiologiques centrales chez les patients cocaïnomanes et d’établir un traitement thérapeutique approprié à leur profil de consommation. L’ensemble des résultats obtenus au cours de cette thèse, ont permis de montrer que le profil d’administration a une grande importance sur les conséquences neurobiologiques de la cocaïne
Pas de résumé en anglais
Advisors/Committee Members: Noble, Florence (thesis director).
Subjects/Keywords: Cocaïne; Cocaine; 612.804 2
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APA (6th Edition):
Puig, S. (2012). Etude intégrée des variations comportementales, neurochimiques et cellulaires de la cocaïne : Analyse des variations à court et à long terme : Importance du profil d’administration et anticipation de l’effet renforçant de la drogue : Integrated study of variations behavioral, neurochemical and cellular of the cocaine. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2012PA05P620
Chicago Manual of Style (16th Edition):
Puig, Stéphanie. “Etude intégrée des variations comportementales, neurochimiques et cellulaires de la cocaïne : Analyse des variations à court et à long terme : Importance du profil d’administration et anticipation de l’effet renforçant de la drogue : Integrated study of variations behavioral, neurochemical and cellular of the cocaine.” 2012. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed January 24, 2020.
http://www.theses.fr/2012PA05P620.
MLA Handbook (7th Edition):
Puig, Stéphanie. “Etude intégrée des variations comportementales, neurochimiques et cellulaires de la cocaïne : Analyse des variations à court et à long terme : Importance du profil d’administration et anticipation de l’effet renforçant de la drogue : Integrated study of variations behavioral, neurochemical and cellular of the cocaine.” 2012. Web. 24 Jan 2020.
Vancouver:
Puig S. Etude intégrée des variations comportementales, neurochimiques et cellulaires de la cocaïne : Analyse des variations à court et à long terme : Importance du profil d’administration et anticipation de l’effet renforçant de la drogue : Integrated study of variations behavioral, neurochemical and cellular of the cocaine. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2012. [cited 2020 Jan 24].
Available from: http://www.theses.fr/2012PA05P620.
Council of Science Editors:
Puig S. Etude intégrée des variations comportementales, neurochimiques et cellulaires de la cocaïne : Analyse des variations à court et à long terme : Importance du profil d’administration et anticipation de l’effet renforçant de la drogue : Integrated study of variations behavioral, neurochemical and cellular of the cocaine. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2012. Available from: http://www.theses.fr/2012PA05P620
Temple University
14.
Craige, Caryne.
Regulation of Cocaine-induced Behaviors and Anxiety Produced by Cocaine Withdrawal through the Serotonin(2C) Receptor.
Degree: PhD, 2013, Temple University
URL: http://digital.library.temple.edu/u?/p245801coll10,239587
► Pharmacology
Cocaine is a powerfully active psychostimulant which exerts its effects through blockade of dopamine, serotonin and norepinephrine transporters and resultant increases in extracellular levels…
(more)
▼ Pharmacology
Cocaine is a powerfully active psychostimulant which exerts its effects through blockade of dopamine, serotonin and norepinephrine transporters and resultant increases in extracellular levels of these neurotransmitters. Much of the focus on cocaine abuse in the literature has been directed towards study of the dopamine system; however, several studies have identified a role for the serotonin system in regulating the rewarding effects of cocaine as well. Specifically, the serotonin 2C (5-HT2C) receptor regulates cocaine-induced alterations in serotonin and dopamine levels in an inhibitory manner, and 5-HT2C receptor agonist treatment attenuates cocaine-induced behaviors like self-administration. In the first aspect of the current thesis study, the effects of activation of 5-HT2C receptors on cocaine-induced conditioned place preference and behavioral sensitization were assessed. It was found that pretreatment with a 5-HT2C receptor agonist, Ro 60-0175, on cocaine (10 mg/kg) conditioning days of the conditioned place preference paradigm, attenuated the development of conditioned place preference in a dose-dependent manner. These results suggest that activation of 5-HT2C receptors inhibits the euphoric effects elicited by cocaine. Behavioral sensitization studies demonstrated that pretreatment with Ro 60-0175 prior to cocaine (10 mg/kg) over a 5 day period attenuated cocaine-induced hyperactivity. When injected with a cocaine challenge injection 10 days after the last cocaine injection, mice pretreated with Ro 60-0175 demonstrated lower levels of locomotor activity as compared to saline pretreated, cocaine-injected mice. This portion of the first study demonstrated that 5-HT2C receptor activity attenuated acute cocaine-induced conditioned reward, hyperactivity and the development of long-term alterations of cocaine exposure, as measured by behavioral sensitization. The second aspect of the current study focused on the regulation of anxiety produced by withdrawal from chronic cocaine administration. Anxiety during cocaine withdrawal is a component of the negative affective state often experienced by cocaine-dependent individuals during abstinence from drug use. Anxiety during cocaine withdrawal is likely to increase an individual's susceptibility to relapse to drug use in alleviation of this negative symptom. Studies have shown a downregulation of the serotonin and dopamine systems during withdrawal that potentially contributes to anxiety symptoms. As the 5-HT2C receptor exerts inhibitory control over both the serotonin and dopamine systems, it was hypothesized that blockade of 5-HT2C receptors would attenuate anxiety-like behavior during cocaine withdrawal. Previous studies have identified co-localization of 5-HT2C receptors on inhibitory gamma-aminobutyric acid (GABA) neurons, thus it was hypothesized that a 5-HT2C receptor-GABA mediated mechanism would be involved in the regulation of anxiety during withdrawal. The dorsal raphe brain region was targeted in these studies, as this region is the primary…
Advisors/Committee Members: Unterwald, Ellen M., Kirby, Lynn;, Bangasser, Debra, Dun, Nae J., Rawls, Scott M., Beck, Sheryl G.;.
Subjects/Keywords: Neurosciences; Pharmacology;
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APA (6th Edition):
Craige, C. (2013). Regulation of Cocaine-induced Behaviors and Anxiety Produced by Cocaine Withdrawal through the Serotonin(2C) Receptor. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,239587
Chicago Manual of Style (16th Edition):
Craige, Caryne. “Regulation of Cocaine-induced Behaviors and Anxiety Produced by Cocaine Withdrawal through the Serotonin(2C) Receptor.” 2013. Doctoral Dissertation, Temple University. Accessed January 24, 2020.
http://digital.library.temple.edu/u?/p245801coll10,239587.
MLA Handbook (7th Edition):
Craige, Caryne. “Regulation of Cocaine-induced Behaviors and Anxiety Produced by Cocaine Withdrawal through the Serotonin(2C) Receptor.” 2013. Web. 24 Jan 2020.
Vancouver:
Craige C. Regulation of Cocaine-induced Behaviors and Anxiety Produced by Cocaine Withdrawal through the Serotonin(2C) Receptor. [Internet] [Doctoral dissertation]. Temple University; 2013. [cited 2020 Jan 24].
Available from: http://digital.library.temple.edu/u?/p245801coll10,239587.
Council of Science Editors:
Craige C. Regulation of Cocaine-induced Behaviors and Anxiety Produced by Cocaine Withdrawal through the Serotonin(2C) Receptor. [Doctoral Dissertation]. Temple University; 2013. Available from: http://digital.library.temple.edu/u?/p245801coll10,239587
Texas A&M University
15.
Valles, Rodrigo, Jr.
Behavioral mechanisms underlying the extinction of cocaine self-administration.
Degree: 2006, Texas A&M University
URL: http://hdl.handle.net/1969.1/3105
► The aim of the present series of experiments was to outline the influence of different doses of cocaine during training, training schedule, training length and…
(more)
▼ The aim of the present series of experiments was to outline the influence of
different doses of
cocaine during training, training schedule, training length and
abstinence duration to modulate subsequent extinction and reinstatement patterns.
Abram Amsel??s general theory of persistence were used to both design and explain
various aspects of these models.
For Experiment 1, rats self-administered
cocaine (0.25, 0.50 or 1.00 mg/kg)
intravenously and were then tested in an extinction preparation using saline infusions (5
days) and then only the stimulus light as the reinforcer (3 days). Experiment 2 examined
schedules by magnitude interactions by training rats on two fixed-ratio (FR) schedules
(FR-1 or FR-10 using either 0.25 or 1.00 mg/kg
cocaine). Animals were tested in an
extinction protocol (10 days; no stimulus light) and subsequently tested for reinstatement
(1 day) that utilized presentations of the stimulus light. Experiment 3 addressed the
effects of training length (15 or 30 days of training using either 0.25 or 1.00 mg/kg
cocaine) using the same protocol as in Experiment 2. Experiment 4 examined the modulation potential of two abstinence lengths (15 or 30 days using either 0.25 or 0.50
mg/kg
cocaine) using the same conditions as Experiment 2.
Experiment 1 indicated the greatest resistance to extinction using the lowest
training dose (0.25 mg/kg). The removal of saline caused an apparent extinction burst
indicative of reward seeking. Experiment 2 showed that animals trained under partial
reinforcement schedules persisted more during extinction. Furthermore, rats trained
using 1.00 were more resistant than those trained with 0.25 mg/kg. Reinstatement of
drug seeking was more pronounced in rats trained using an FR-10 schedule. Experiment
3 indicated greater resistance to extinction in rats trained for 15 versus 30 days. Rats
trained on 0.50 mg/kg for 30 days showed less cue-induced reinstatement than those
trained for 15 days. Experiment 4 showed increased resistance to extinction when rats
were trained on 0.25 mg/kg and forced to abstain for 30 versus 15 days. Directionally
opposite effects were apparent in groups trained with 0.50 mg/kg. Reinstatement data
indicated greater responsivity to cues by animals abstaining for 30 versus 15 days.
Advisors/Committee Members: Nation, Jack R (advisor), Bratton, Gerald R (committee member), Setlow, Barry (committee member), Wellman, Paul J (committee member).
Subjects/Keywords: Extinction; Cocaine
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APA (6th Edition):
Valles, Rodrigo, J. (2006). Behavioral mechanisms underlying the extinction of cocaine self-administration. (Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/3105
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Valles, Rodrigo, Jr. “Behavioral mechanisms underlying the extinction of cocaine self-administration.” 2006. Thesis, Texas A&M University. Accessed January 24, 2020.
http://hdl.handle.net/1969.1/3105.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Valles, Rodrigo, Jr. “Behavioral mechanisms underlying the extinction of cocaine self-administration.” 2006. Web. 24 Jan 2020.
Vancouver:
Valles, Rodrigo J. Behavioral mechanisms underlying the extinction of cocaine self-administration. [Internet] [Thesis]. Texas A&M University; 2006. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/1969.1/3105.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Valles, Rodrigo J. Behavioral mechanisms underlying the extinction of cocaine self-administration. [Thesis]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/3105
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Boston University
16.
Culp, Jenna L.
Cocaine use, treatment retention and opioid abstinence at six months in a coordinated primary care and substance abuse treatment clinic among opioid-dependent patients treated with buprenorphine.
Degree: MA, Medical Sciences, 2012, Boston University
URL: http://hdl.handle.net/2144/12336
► Cocaine use among opioid dependent persons is common, with an estimated 40 to 70% of those seeking treatment for opioid dependence, also using cocaine (Sullivan…
(more)
▼ Cocaine use among opioid dependent persons is common, with an estimated 40 to 70% of those seeking treatment for opioid dependence, also using cocaine (Sullivan et al., 2011 ). The effects of cocaine use on treatment outcomes for those seeking medication assisted treatment (MAT) for opioid
dependence are not well understood. Buprenorphine, prescribed under the brand name Suboxone, has recently emerged as a convenient, effective method of MAT. The Facilitated Access to Substance Abuse Treatment with Prevention And Treatment of HIV (FAST PATH) program at Boston Medical Center, is a research study to provide substance abuse treatment along with primary care and HIV risk-reduction counseling to those afflicted with these epidemics. The objective of this study was to determine the association of cocaine use with treatment retention and opioid abstinence at six months for patients receiving
buprenorphine in the FAST PATH program.
A prospective cohort study was conducted on 116 patients enrolled in the FAST PATH program through 02/01/2012. Assessments were conducted at baseline and six months to evaluate the association between baseline cocaine use and treatment retention as well as opioid abstinence at six months. Baseline cocaine use was measured by either any urine toxicology screen positive for cocaine prior to study enrollment or 30 day self-reported cocaine use on the initial assessment.
Of the 116 participants, 39% were positive for cocaine use at baseline and 52% were HIV positive. Baseline cocaine use had no effect significant on treatment retention or opioid abstinence at six months. Among all the participant characteristics measured, there were no significant differences between the cocaine positive (n=45) and cocaine negative (n=71) groups. In adjusted analysis, age was the only covariate which was significant at predicting the odds of treatment retention or opioid abstinence with a 1.11 (p-value = 0.0003) and 1.08 (p-value = 0.02) greater odds of each, respectively. Although cocaine use
did not affect the dependent variables, integrated substance abuse and primary care clinics utilizing buprenorphine are a rich area of future research. Specifically, subsequent studies should determine how varied groups of opioid dependent persons perform within this framework, and the underlying characteristics moderating their outcomes.
Subjects/Keywords: Opioid dependence; Cocaine; FAST PATH
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APA (6th Edition):
Culp, J. L. (2012). Cocaine use, treatment retention and opioid abstinence at six months in a coordinated primary care and substance abuse treatment clinic among opioid-dependent patients treated with buprenorphine. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/12336
Chicago Manual of Style (16th Edition):
Culp, Jenna L. “Cocaine use, treatment retention and opioid abstinence at six months in a coordinated primary care and substance abuse treatment clinic among opioid-dependent patients treated with buprenorphine.” 2012. Masters Thesis, Boston University. Accessed January 24, 2020.
http://hdl.handle.net/2144/12336.
MLA Handbook (7th Edition):
Culp, Jenna L. “Cocaine use, treatment retention and opioid abstinence at six months in a coordinated primary care and substance abuse treatment clinic among opioid-dependent patients treated with buprenorphine.” 2012. Web. 24 Jan 2020.
Vancouver:
Culp JL. Cocaine use, treatment retention and opioid abstinence at six months in a coordinated primary care and substance abuse treatment clinic among opioid-dependent patients treated with buprenorphine. [Internet] [Masters thesis]. Boston University; 2012. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/2144/12336.
Council of Science Editors:
Culp JL. Cocaine use, treatment retention and opioid abstinence at six months in a coordinated primary care and substance abuse treatment clinic among opioid-dependent patients treated with buprenorphine. [Masters Thesis]. Boston University; 2012. Available from: http://hdl.handle.net/2144/12336
University of South Florida
17.
Haire, Kambria.
Elucidation of the Role of Poly(ADP-Ribose) Polymerase in Drug-Induced Toxicity.
Degree: 2015, University of South Florida
URL: https://scholarcommons.usf.edu/etd/5959
► Drug toxicity may cause liver injury, resulting in damage to cells and tissues. This damage can lead to cytotoxic events that may result in an…
(more)
▼ Drug toxicity may cause liver injury, resulting in damage to cells and tissues. This damage can lead to cytotoxic events that may result in an activation of poly (ADP-ribose) polymerase (PARP). A study was conducted to determine if cocaine and acetaminophen toxicity lead to DNA damage and to the activation of the repair protein, PARP in the liver using the hepatotoxicants: cocaine and acetaminophen (APAP).
A dose-response analysis for cocaine concluded that a dose as low as 20 mg/kg resulted in elevated ALT levels. A higher dose of 60 mg/kg was tested for analyses but resulted in severe hemorrhaging. The dose-response analyses for APAP resulted in no elevated liver enzyme levels for a 75 mg/kg and 150 mg/kg dose. A dose of 50 mg/kg for cocaine, and a dose of 300 mg/kg for APAP were used to analyze temporal trends for both toxicants. Both cocaine and APAP produced incremental increases in ALT at the 2 hour, 6 hour, 18 hour, and 24 hour time points, respectively. PARP activity analysis for cocaine measured the highest activity at the 2hr and 6hr time points. PARP analysis for acetaminophen measured gradual increases until the 18 hour time point where the highest level of PARP activity was measured.
A PARP inhibition analysis was conducted with cocaine and (APAP) to understand the impact of a PARP inhibitor, 1,5-dihydroxyisoquinoline (DIQ), on PARP activity in the liver. A 50 mg/kg dose of cocaine or a 300 mg/kg dose of APAP was administered, followed by a 10 mg/kg dose of DIQ at 1) the time of initial toxicant dose (0 hour), or 2) 1 hour after initial toxicant dose (1hr). The PARP inhibition analysis for cocaine and APAP was conducted at 6 and 18 hours post initial dose, respectively, when the highest levels of PARP were observed. Inhibition analyses determined that ALT declined significantly when DIQ was administered immediately following the initial toxicant dose for both toxicants. DIQ administered 1 hr after initial toxicant dose resulted in slightly higher ALT than the 0 hr time point. Decreases in PARP activity were observed at the 0 hr time point, with slightly higher PARP levels observed at the 1 hr time point. Decreased PARP activity was observed following DIQ treatment with both, a concurrent drug treatment and treatment following drug administration. Cocaine and APAP treatment did not cause DNA fragmentation. A liver glutathione (GSH) analysis conducted for cocaine and APAP did not correlate with DIQ alteration of PARP activity. The mechanism of DIQ effects on drug-induced hepatotoxicity appears to be GSH independent. DIQ was effective in reducing drug-induced hepatotoxicity and preserving organ function.
Subjects/Keywords: PARP; Heptotoxicity; Cocaine; Acetaminophen; Toxicology
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APA (6th Edition):
Haire, K. (2015). Elucidation of the Role of Poly(ADP-Ribose) Polymerase in Drug-Induced Toxicity. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/5959
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Haire, Kambria. “Elucidation of the Role of Poly(ADP-Ribose) Polymerase in Drug-Induced Toxicity.” 2015. Thesis, University of South Florida. Accessed January 24, 2020.
https://scholarcommons.usf.edu/etd/5959.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Haire, Kambria. “Elucidation of the Role of Poly(ADP-Ribose) Polymerase in Drug-Induced Toxicity.” 2015. Web. 24 Jan 2020.
Vancouver:
Haire K. Elucidation of the Role of Poly(ADP-Ribose) Polymerase in Drug-Induced Toxicity. [Internet] [Thesis]. University of South Florida; 2015. [cited 2020 Jan 24].
Available from: https://scholarcommons.usf.edu/etd/5959.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Haire K. Elucidation of the Role of Poly(ADP-Ribose) Polymerase in Drug-Induced Toxicity. [Thesis]. University of South Florida; 2015. Available from: https://scholarcommons.usf.edu/etd/5959
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Minnesota
18.
McCall, Nora.
G protein-gated potassium channels in ventral tegmental area dopamine neurons temper behavioral sensitivity to cocaine.
Degree: PhD, Neuroscience, 2019, University of Minnesota
URL: http://hdl.handle.net/11299/202436
► Drugs of abuse share the ability to enhance dopamine (DA) release in the mesocorticolimbic system. This increase in DA is thought to drive persistent adaptations…
(more)
▼ Drugs of abuse share the ability to enhance dopamine (DA) release in the mesocorticolimbic system. This increase in DA is thought to drive persistent adaptations in the brain and behavior that contribute to the progression of addiction. One such adaptation is a cocaine exposure-induced suppression of G protein-dependent inhibitory signaling in DA neurons of the ventral tegmental area (VTA), a cell population important for reward-related behavior. This cocaine-induced adaptation involves the internalization of G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, a key contributor to inhibitory G protein pathways that normally temper DA neurotransmission in the mesocorticolimbic system. Dopamine 2 receptor (D2R) activation mediates this adaptation. While methamphetamine, another psychostimulant, can induce a similar adaptation in inhibitory G protein signaling, other drugs of abuse, i.e. morphine, are unable to induce a GIRK channel adaptation. Thus, inhibitory G protein signaling in VTA DA neurons could be important for tempering the behavioral response to cocaine, and could represent an inhibitory “barrier” to addiction. The goal of this thesis research is to understand the impact of GIRK channel activity signaling on behavioral sensitivity to cocaine. The work in this thesis tests the hypothesis that the strength of inhibitory G protein signaling in VTA DA neurons is inversely related to behavioral sensitivity to cocaine. This hypothesis predicts decreasing GIRK channel activity in DA neurons will increase behavioral sensitivity to cocaine. To test this, a genetic strategy was employed, to ablate GIRK channels in DA neurons using DATCre(+):Girk2fl/fl mice. The strength of two significant G protein receptor-dependent signaling dependent on GIRK channels were significantly reduced in a dopamine neuron-specific manner. DATCre(+):Girk2fl/fl mice displayed increased locomotor responding to both acute and repeated cocaine, as well as increased responding for, and intake of, cocaine in intravenous self-administration. The DATCre(+):Girk2fl/fl manipulation parallels the cocaine-induced suppression of GIRK-dependent signaling in VTA DA neurons, and suggests the GIRK channel in DA neurons temper behavioral sensitivity to cocaine. This hypothesis was further tested in a VTA-specific manner using a Cre-dependent viral approach, overexpressing GIRK channels with opposing functional roles. The overexpression of GIRK2 increased inhibitory G protein signaling and decreased cocaine-induced locomotion, while conversely, overexpression of GIRK3 decreased inhibitory G protein signaling and increased cocaine-induced locomotion. Overall, this supports the hypothesis GIRK channel activity in VTA DA neurons tempers behavioral sensitivity to drugs of abuse. In addition to addiction, VTA DA neurons have been implicated in negative affective behaviors, notably following stress. Interestingly, manipulating GIRK channel activity did not alter depression- and anxiety-related behavior, suggests that inhibitory signaling in VTA DA…
Subjects/Keywords: cocaine; dopamine; GIRK; VTA
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APA ·
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APA (6th Edition):
McCall, N. (2019). G protein-gated potassium channels in ventral tegmental area dopamine neurons temper behavioral sensitivity to cocaine. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/202436
Chicago Manual of Style (16th Edition):
McCall, Nora. “G protein-gated potassium channels in ventral tegmental area dopamine neurons temper behavioral sensitivity to cocaine.” 2019. Doctoral Dissertation, University of Minnesota. Accessed January 24, 2020.
http://hdl.handle.net/11299/202436.
MLA Handbook (7th Edition):
McCall, Nora. “G protein-gated potassium channels in ventral tegmental area dopamine neurons temper behavioral sensitivity to cocaine.” 2019. Web. 24 Jan 2020.
Vancouver:
McCall N. G protein-gated potassium channels in ventral tegmental area dopamine neurons temper behavioral sensitivity to cocaine. [Internet] [Doctoral dissertation]. University of Minnesota; 2019. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/11299/202436.
Council of Science Editors:
McCall N. G protein-gated potassium channels in ventral tegmental area dopamine neurons temper behavioral sensitivity to cocaine. [Doctoral Dissertation]. University of Minnesota; 2019. Available from: http://hdl.handle.net/11299/202436
University of Texas Southwestern Medical Center
19.
Jester, Bryan Elliott.
Examining the Relationship Between Impulsive Personalities and Neural Functioning in Cocaine-Addicted Participants.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1308
► BACKGROUND: Those who suffer from addiction are unable to discontinue use despite serious consequences affecting their social, professional, and family lives. Individuals who suffer from…
(more)
▼ BACKGROUND: Those who suffer from addiction are unable to discontinue use despite serious consequences affecting their social, professional, and family lives. Individuals who suffer from the disorder often alienate themselves from loved ones and lose their jobs. Addiction involves continuing a behavior despite severe negative consequences. Numerous studies have identified a relationship between impulsivity and the development of substance abuse. This study examines the relationship of impulsive personality facets and neural functioning associated with inhibition.
SUBJECTS: The study sample included 24 healthy control participants and 56
cocaine-addicted participants. Participants ranged in age from 25 to 54 years old with a mean age of 43.27 (±SD 7.84). The group was comprised of 68 male and 12 female participants, 28.7% self identified as Caucasian, 66.3% African American, 3.8% Hispanic, and 1.3% Asian/Other. Healthy controls and
cocaine-addicted participants were similar in age and race but differed in gender (p= .02). The control group had 17 males and 7 females while the
cocaine-addicted group had 51 males and 5 females.
METHODS: Demographic information was gathered for all participants. Each participant also completed a Neuroticism Extroversion and Openness (NEO) personality measure and Temperament and Character Inventory (TCI), Structured Clinical Interview for DSM-IV (SCID), Wechsler Test of Adult Reading (WTAR). They then performed the stop signal task (SST) during functional magnetic resonance imaging (fMRI) to gather data on neural activation during Stop-Success (SS) and Stop-Failure (SF). fMRI data was analyzed using FSL imaging software. All statistics were run with SPSS software. Functional ROIs were identified and analyzed in fMRI Expert Analysis Tool query (FEATqueary) to gather data on each participantÕs change in blood oxygen level dependent (BOLD) activation during Stop-Success (SS) and Stop-Failure (SF). Impulsive personality facets were then used to identify relationships between BOLD activations of the ROIs.
RESULTS: Between group comparisons found significant differences in mean scores on all of the impulsive personality facets except for Exploratory Excitability and Persistence from the TCI, and Excitement Seeking from the NEO. Neuroimaging results are similar to other studies utilizing the SST finding changes in activation of the middle frontal gyrus, superior frontal gyrus, cingulate gyrus, medial frontal gyrus, insula, caudate and supramarginal gyrus during Stop-Failure; and superior parietal lobule, middle frontal gyrus, precuneus, supramarginal gyrus, inferior temporal gyrus, and middle occipital gyrus during Stop-Success. However, no differences in BOLD activation between groups were observed. Numerous relationships were identified between the personality facets and BOLD activation of the regions of interest (ROIs). To further elucidate this relationship between neural functioning and personality a principal component analysis (PCA) was conducted on all eleven personality facets. The…
Advisors/Committee Members: Adinoff, Bryon H., North, Carol S., Spence, Jeffrey.
Subjects/Keywords: Impulsive Behavior; Cocaine-Related Disorders
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APA (6th Edition):
Jester, B. E. (2013). Examining the Relationship Between Impulsive Personalities and Neural Functioning in Cocaine-Addicted Participants. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1308
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jester, Bryan Elliott. “Examining the Relationship Between Impulsive Personalities and Neural Functioning in Cocaine-Addicted Participants.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed January 24, 2020.
http://hdl.handle.net/2152.5/1308.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jester, Bryan Elliott. “Examining the Relationship Between Impulsive Personalities and Neural Functioning in Cocaine-Addicted Participants.” 2013. Web. 24 Jan 2020.
Vancouver:
Jester BE. Examining the Relationship Between Impulsive Personalities and Neural Functioning in Cocaine-Addicted Participants. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/2152.5/1308.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jester BE. Examining the Relationship Between Impulsive Personalities and Neural Functioning in Cocaine-Addicted Participants. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1308
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Rutgers University
20.
Pantazis, Caroline B., 1990-.
Lateral septum and lateral hypothalamus orexin neurons mediate motivation for cocaine through interactions with the mesolimbic dopamine system.
Degree: PhD, Addiction, 2019, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/60914/
► Drug addiction is a disorder characterized by pathological motivation for drug. Our laboratory has recently developed a behavioral economics (BE) paradigm that uniquely assesses demand…
(more)
▼ Drug addiction is a disorder characterized by pathological motivation for drug. Our laboratory has recently developed a behavioral economics (BE) paradigm that uniquely assesses demand for drugs of abuse. Animals’ individual lever-pressing data can be fitted to demand curves to determine two important measures of cocaine demand: baseline consumption (Q0) and motivation (α). As α is the slope of the demand curve, it inversely scales with motivation, such that animals with greater demand elasticity (α) have lower motivation for cocaine. Here, we utilized our BE paradigm with pharmacological, morpholino antisense, and retrograde tracing approaches and determined that lateral septum (LS) and lateral hypothalamus (LH) orexin neurons are important neuronal populations for cocaine demand elasticity (α).
We demonstrate that inhibiting LS reduced motivation (increased demand elasticity; α) and that the benzodiazepine diazepam blocked this effect, pointing to opposing roles of the two manipulations on ventral tegmental area (VTA) dopamine signaling. The two manipulations were similarly found to be anxiolytic, indicating that changes in drug taking occurred independently of effects on anxiety. Similarly, we show that orexin signaling contributes to motivation for cocaine (α) and that the involvement of orexin in motivated drug taking is mediated primarily by orexin neurons in LH. Animals sacrificed after BE had greater expression of orexin neurons in LH, and unilateral knockdown of LH orexin cells attenuated motivation during BE. The number of spared LH orexin neurons predicted α value in antisense-infused animals and in animals sacrificed two weeks after BE testing. We then blocked orexin-1 receptor signaling in VTA using the oreceptor antagonist SB-334867 (SB) and found that intra-VTA SB reduced motivation. The effects of SB specifically occurred in animals trained and tested on BE with cues and removing cocaine-paired cues reduced SB efficacy. Finally, using retrograde tract tracing, we observed that a greater proportion of LH orexin neurons project to VTA than do other subregions of the orexin cell field.
Collectively, these studies implicate two important neuronal populations in motivation for cocaine and indicate that both LS and LH orexin connections to the mesolimbic dopamine system mediate their effects on motivation.
Advisors/Committee Members: Aston-Jones, Gary (chair), School of Graduate Studies.
Subjects/Keywords: Neuroscience; Cocaine abuse – Prevention; Neuropharmacology
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APA ·
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APA (6th Edition):
Pantazis, Caroline B., 1. (2019). Lateral septum and lateral hypothalamus orexin neurons mediate motivation for cocaine through interactions with the mesolimbic dopamine system. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/60914/
Chicago Manual of Style (16th Edition):
Pantazis, Caroline B., 1990-. “Lateral septum and lateral hypothalamus orexin neurons mediate motivation for cocaine through interactions with the mesolimbic dopamine system.” 2019. Doctoral Dissertation, Rutgers University. Accessed January 24, 2020.
https://rucore.libraries.rutgers.edu/rutgers-lib/60914/.
MLA Handbook (7th Edition):
Pantazis, Caroline B., 1990-. “Lateral septum and lateral hypothalamus orexin neurons mediate motivation for cocaine through interactions with the mesolimbic dopamine system.” 2019. Web. 24 Jan 2020.
Vancouver:
Pantazis, Caroline B. 1. Lateral septum and lateral hypothalamus orexin neurons mediate motivation for cocaine through interactions with the mesolimbic dopamine system. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2020 Jan 24].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60914/.
Council of Science Editors:
Pantazis, Caroline B. 1. Lateral septum and lateral hypothalamus orexin neurons mediate motivation for cocaine through interactions with the mesolimbic dopamine system. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60914/
Nelson Mandela Metropolitan University
21.
Plumb, Sarah.
The art of addiction : a phenomenological study of the lived experiences of cocaine dependents.
Degree: Faculty of Health Sciences, 2009, Nelson Mandela Metropolitan University
URL: http://hdl.handle.net/10948/902
► Addiction is a complex social phenomenon resulting from psychological and physiological dependence. The aim of the study was to create a clinical impression of the…
(more)
▼ Addiction is a complex social phenomenon resulting from psychological and physiological dependence. The aim of the study was to create a clinical impression of the lived experiences of cocaine dependents. A transcendental phenomenological approach was used to elicit the essence of addiction as experienced by the participants. Theoretical sampling ensured relevant participants were selected through haphazard sampling procedures. Data was collected through the use of biographical questionnaires and individual, semi-structured interviews with three cocaine dependents. Data was processed according to the four phenomenological principles epoche, phenomenological reduction, imaginative variation and synthesis using Tesch’s eight steps. The essence of cocaine dependency is contained in the psychological experiences of the drug which define and perpetuate that addiction. The psychological addiction develops prior to physical dependence resulting in an entrenched addiction before treatment is sought by the cocaine dependents.
Subjects/Keywords: Cocaine abuse; Cocaine – Social aspects; Drugs – Physiological effect
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APA (6th Edition):
Plumb, S. (2009). The art of addiction : a phenomenological study of the lived experiences of cocaine dependents. (Thesis). Nelson Mandela Metropolitan University. Retrieved from http://hdl.handle.net/10948/902
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Plumb, Sarah. “The art of addiction : a phenomenological study of the lived experiences of cocaine dependents.” 2009. Thesis, Nelson Mandela Metropolitan University. Accessed January 24, 2020.
http://hdl.handle.net/10948/902.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Plumb, Sarah. “The art of addiction : a phenomenological study of the lived experiences of cocaine dependents.” 2009. Web. 24 Jan 2020.
Vancouver:
Plumb S. The art of addiction : a phenomenological study of the lived experiences of cocaine dependents. [Internet] [Thesis]. Nelson Mandela Metropolitan University; 2009. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/10948/902.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Plumb S. The art of addiction : a phenomenological study of the lived experiences of cocaine dependents. [Thesis]. Nelson Mandela Metropolitan University; 2009. Available from: http://hdl.handle.net/10948/902
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
22.
Carreira Franceschi, Maria Beatriz.
Characterization of Histone Deacetylase 4 and Histone Deacetylase 5 in Cocaine-Related Behaviors.
Degree: 2016, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/5304
► In recent years a focus on epigenetic mechanisms as mediators of cocaine-related behavioral, structural and functional plasticity has developed. One family of epigenetic molecules that…
(more)
▼ In recent years a focus on epigenetic mechanisms as mediators of
cocaine-related behavioral, structural and functional plasticity has developed. One family of epigenetic molecules that may underlie
cocaine behavioral and functional changes is the histone deacetylase family that acts to mediate transcriptional repression. The class IIa subgroup of histone deacetylases is poised as an intracellular signal detector and effector by virtue of their ability to shuttle subcellularly in a dynamic and activity-dependent manner primarily driven by phosphorylation status of the protein at multiple residues. The overlying goal of this thesis was to two-faceted: to characterize the regulation of two class IIa members, HDAC4 and HDAC5, by
cocaine-mediated signaling and to characterize the role of HDAC4 and HDAC5 in
cocaine-associated behavioral plasticity. We report the regulation of phosphorylation and localization of HDAC4 and HDAC5 is in opposition. HDAC5 is dephosphorylated and accumulated in the nuclear compartment in response to
cocaine, dopamine dependent signaling and cAMP activity. Meanwhile, we observe that HDAC4 is weakly dephosphorylated by cAMP activity in culture but weakly phosphorylated in vivo. These findings encouraged the analysis of function of these highly homologous class members. We assessed the function of HDAC4 and HDAC5 in the nucleus accumbens, a critical region for reward, by over-expressing wildtype and nuclear variants by targeted viral-mediated gene transfer. We report an attenuation of
cocaine reward learning by nuclear HDAC5 but not wildtype or HDAC4 over-expression. We further analyzed the role of HDAC5 in self-administration behavior and report an effect of nuclear HDAC5, but not wildtype, on models of reinstatement of seeking, a preclinical model of relapse. These effects were observed in the absence of an effect on intake, sensitivity or motivation to self-administer. Because HDAC4 and HDAC5 bind nuclear transcriptional regulators to exert transcriptional repression of target genes we analyzed the dependence of nuclear HDAC5 on interacting with MEF2, a primary binding partners, and report that this interaction is likely required for modulating reinstatement of seeking but dispensable for
cocaine reward. Taken together, these findings highlight the role of nuclear HDAC5 but not HDAC4 to limit
cocaine reward and aspects of
cocaine addiction-like behavior.
Advisors/Committee Members: Self, David W., Cowan, Christopher W., Huber, Kimberly M., Rothenfluh, Adrian.
Subjects/Keywords: Cocaine; Cocaine-Related Disorders; Histone Deacetylases; Nucleus Accumbens; Reward; Self Administration
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APA (6th Edition):
Carreira Franceschi, M. B. (2016). Characterization of Histone Deacetylase 4 and Histone Deacetylase 5 in Cocaine-Related Behaviors. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/5304
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Carreira Franceschi, Maria Beatriz. “Characterization of Histone Deacetylase 4 and Histone Deacetylase 5 in Cocaine-Related Behaviors.” 2016. Thesis, University of Texas Southwestern Medical Center. Accessed January 24, 2020.
http://hdl.handle.net/2152.5/5304.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Carreira Franceschi, Maria Beatriz. “Characterization of Histone Deacetylase 4 and Histone Deacetylase 5 in Cocaine-Related Behaviors.” 2016. Web. 24 Jan 2020.
Vancouver:
Carreira Franceschi MB. Characterization of Histone Deacetylase 4 and Histone Deacetylase 5 in Cocaine-Related Behaviors. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2016. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/2152.5/5304.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Carreira Franceschi MB. Characterization of Histone Deacetylase 4 and Histone Deacetylase 5 in Cocaine-Related Behaviors. [Thesis]. University of Texas Southwestern Medical Center; 2016. Available from: http://hdl.handle.net/2152.5/5304
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Georgia Tech
23.
Javanmard, Sahar.
Synthesis and pharmacology of site-specific cocaine abuse treatment agents.
Degree: PhD, Chemistry, 2002, Georgia Tech
URL: http://hdl.handle.net/1853/30952
Subjects/Keywords: Cocaine habit Treatment; Cocaine Toxicology
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APA (6th Edition):
Javanmard, S. (2002). Synthesis and pharmacology of site-specific cocaine abuse treatment agents. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/30952
Chicago Manual of Style (16th Edition):
Javanmard, Sahar. “Synthesis and pharmacology of site-specific cocaine abuse treatment agents.” 2002. Doctoral Dissertation, Georgia Tech. Accessed January 24, 2020.
http://hdl.handle.net/1853/30952.
MLA Handbook (7th Edition):
Javanmard, Sahar. “Synthesis and pharmacology of site-specific cocaine abuse treatment agents.” 2002. Web. 24 Jan 2020.
Vancouver:
Javanmard S. Synthesis and pharmacology of site-specific cocaine abuse treatment agents. [Internet] [Doctoral dissertation]. Georgia Tech; 2002. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/1853/30952.
Council of Science Editors:
Javanmard S. Synthesis and pharmacology of site-specific cocaine abuse treatment agents. [Doctoral Dissertation]. Georgia Tech; 2002. Available from: http://hdl.handle.net/1853/30952
University of Florida
24.
Mccann, Sarah.
Latent Growth Curve Analyses of the Development of Executive Functions in a Prospective, Longitudinal Cohort of Children with Prenatal Cocaine Exposure.
Degree: PhD, Psychology - Clinical and Health Psychology, 2010, University of Florida
URL: http://ufdc.ufl.edu/UFE0041899
► Animal studies demonstrate prenatal exposure to cocaine causes disruption of the neurotrophic roles of monoaminergic transmitters during early development, which, in turn, affects the cortical…
(more)
▼ Animal studies demonstrate prenatal exposure to
cocaine causes disruption of the neurotrophic roles of monoaminergic transmitters during early development, which, in turn, affects the cortical neuronal development of specific brain regions, including prefrontal cortex. In humans, this brain area is implicated in executive function (EF), a set of cognitive processes that are posited to subserve goal-directed behavior. Significant differences in EF between children with prenatal
cocaine exposure (PCE) and well-matched comparison groups have not been consistently found. Within a longitudinal context, there have been no studies investigating the potential effect of PCE on the developmental trajectory of EF. Participants were children of pregnant women who were prospectively enrolled at birth in a longitudinal study of the developmental effects of PCE. At study enrollment, which generally occurred during pregnancy,
cocaine-using mothers were matched to non-
cocaine using mothers on race, socioeconomic status, parity and location of prenatal care. Both groups were predominately poor and African American and did not differ by child sex. At birth, PCE group had higher levels of other prenatal drug exposures (alcohol, tobacco, and marijuana), shorter gestational ages, and smaller head circumferences. Measures of EF (inhibition, working memory, and shifting) were obtained by blinded examiners when the children were ages 7, 10one half, and 12one half years. There were no group differences between the PCE children (n = 120) and non-exposed children (n = 116) with regard to cross-sectional performance on measures of EF at any time point. Univariate latent growth models were used to investigate the effect of amount of PCE as well as pre- and post-natal characteristics of the child and the environment (i.e., birth head circumference, gender, quality of the caregiving environment) on the developmental trajectory of inhibition, working memory, and shifting. Results indicated no direct effect of PCE on the initial performance or the development of EF over time. Smaller birth head circumference negatively predicted the inhibitory and working memory skills at age 7 as well as worse development of inhibitory skills over time. Additionally, a better quality home environment positively predicted working memory ability at age 7 years, though the home environment did not predict the developmental trajectory of any EF over time. ( en )
Advisors/Committee Members: Heaton, Shelley C. (committee chair), Johnson, James H. (committee member), Fennell, Eileen B. (committee member), Eyler, Fonda D. (committee member).
Subjects/Keywords: Alcohols; Business executives; Child development; Child psychology; Cocaine; Fetal cocaine exposure; Head circumference; Memory interference; Modeling; Working memory; cocaine, cognition, development
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APA (6th Edition):
Mccann, S. (2010). Latent Growth Curve Analyses of the Development of Executive Functions in a Prospective, Longitudinal Cohort of Children with Prenatal Cocaine Exposure. (Doctoral Dissertation). University of Florida. Retrieved from http://ufdc.ufl.edu/UFE0041899
Chicago Manual of Style (16th Edition):
Mccann, Sarah. “Latent Growth Curve Analyses of the Development of Executive Functions in a Prospective, Longitudinal Cohort of Children with Prenatal Cocaine Exposure.” 2010. Doctoral Dissertation, University of Florida. Accessed January 24, 2020.
http://ufdc.ufl.edu/UFE0041899.
MLA Handbook (7th Edition):
Mccann, Sarah. “Latent Growth Curve Analyses of the Development of Executive Functions in a Prospective, Longitudinal Cohort of Children with Prenatal Cocaine Exposure.” 2010. Web. 24 Jan 2020.
Vancouver:
Mccann S. Latent Growth Curve Analyses of the Development of Executive Functions in a Prospective, Longitudinal Cohort of Children with Prenatal Cocaine Exposure. [Internet] [Doctoral dissertation]. University of Florida; 2010. [cited 2020 Jan 24].
Available from: http://ufdc.ufl.edu/UFE0041899.
Council of Science Editors:
Mccann S. Latent Growth Curve Analyses of the Development of Executive Functions in a Prospective, Longitudinal Cohort of Children with Prenatal Cocaine Exposure. [Doctoral Dissertation]. University of Florida; 2010. Available from: http://ufdc.ufl.edu/UFE0041899
University of Kentucky
25.
Smith, Christine Elizabeth.
SPLENDOR IN THE BLUEGRASS: THE POLICING OF DRUG RELATED CRIME IN LEXINGTON, KENTUCKY.
Degree: 2010, University of Kentucky
URL: http://uknowledge.uky.edu/gradschool_theses/12
► This project is designed as a case study investigating the relationship and practices between residents and police officers in the William Wells Brown neighborhood of…
(more)
▼ This project is designed as a case study investigating the relationship and practices between residents and police officers in the William Wells Brown neighborhood of Lexington, Kentucky toward the issue of drug-related crime. Employing Michel Foucault‘s work on governmentality and his concept of Splendor, I explore how governance is practiced within the daily negotiations of the WWB neighborhood. I approach this project through the lens of policing because some residents, especially those who comprise the William Wells Brown Neighborhood Association, form a limited partnership with the police department in combating the threat of drug crime in the neighborhood. Drug-related crime is defined as the purchasing, selling or using of illegal drugs. In my research, the illegal drug most commonly referred to is crack cocaine. Through my analysis, I explore the importance of visual appearances and spatial regulation in the policing of individuals.
Subjects/Keywords: Policing; community; crack cocaine; governmentality; splendor; Geography
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APA (6th Edition):
Smith, C. E. (2010). SPLENDOR IN THE BLUEGRASS: THE POLICING OF DRUG RELATED CRIME IN LEXINGTON, KENTUCKY. (Masters Thesis). University of Kentucky. Retrieved from http://uknowledge.uky.edu/gradschool_theses/12
Chicago Manual of Style (16th Edition):
Smith, Christine Elizabeth. “SPLENDOR IN THE BLUEGRASS: THE POLICING OF DRUG RELATED CRIME IN LEXINGTON, KENTUCKY.” 2010. Masters Thesis, University of Kentucky. Accessed January 24, 2020.
http://uknowledge.uky.edu/gradschool_theses/12.
MLA Handbook (7th Edition):
Smith, Christine Elizabeth. “SPLENDOR IN THE BLUEGRASS: THE POLICING OF DRUG RELATED CRIME IN LEXINGTON, KENTUCKY.” 2010. Web. 24 Jan 2020.
Vancouver:
Smith CE. SPLENDOR IN THE BLUEGRASS: THE POLICING OF DRUG RELATED CRIME IN LEXINGTON, KENTUCKY. [Internet] [Masters thesis]. University of Kentucky; 2010. [cited 2020 Jan 24].
Available from: http://uknowledge.uky.edu/gradschool_theses/12.
Council of Science Editors:
Smith CE. SPLENDOR IN THE BLUEGRASS: THE POLICING OF DRUG RELATED CRIME IN LEXINGTON, KENTUCKY. [Masters Thesis]. University of Kentucky; 2010. Available from: http://uknowledge.uky.edu/gradschool_theses/12
Temple University
26.
Lamarre, Neil Stanley.
Utilizing novel dose equivalence methodologies to examine cocaine's effects on the vasculature.
Degree: PhD, 2013, Temple University
URL: http://digital.library.temple.edu/u?/p245801coll10,221180
► Pharmacology
UTILIZING NOVEL DOSE EQUIVALENCE METHODOLOGIES TO EXAMINE COCAINE'S EFFECTS ON THE VASCULATURE Neil S. Lamarre Doctor of Philosophy Temple University School of Medicine, 2013…
(more)
▼ Pharmacology
UTILIZING NOVEL DOSE EQUIVALENCE METHODOLOGIES TO EXAMINE COCAINE'S EFFECTS ON THE VASCULATURE Neil S. Lamarre Doctor of Philosophy Temple University School of Medicine, 2013 Doctoral Advisory Committee Chair: Ronald J. Tallarida, Ph.D. Cocaine abuse and addiction is a serious health problem, resulting in thousands of emergency room visits and deaths each year in the United States. It is particularly toxic to the cardiovascular system, including deleterious effects on the peripheral vasculature. These effects are not well understood, but evidence suggests chronic cocaine use may lead to endothelial dysfunction, thereby increasing relative risk of a number of other cardiovascular diseases including stroke, aneurysm, myocardial infarction, hypertension, etc. Data from our lab, and others, suggest that the presence of a functional endothelium has a dramatic effect on the contractility of the rat aorta that is agonist-specific. Attenuation of this endothelium-dependent vasodilatory component of agonist action is a primary feature of endothelial dysfunction. We have utilized dose equivalence theory to calculate the dose response relationship for the endothelium-dependent vasodilatory component of an agonist causing overt vasoconstriction. This component cannot be measured directly, but our novel methodology allows us to quantitate agonist-specific impairment of vasodilation, and describe it using the familiar parameters of the dose response curve. Another strength of this method, relative to currently used in vitro methods, is that it also avoids the confounding variable of a second agonist used to produce the initial vasoconstriction. To validate the methodology, a pilot study was performed examining the endothelial dysfunction in STZ-induced diabetic rats, as a positive control for endothelial dysfunction. Interestingly, this treatment showed impairment in the endothelium-dependent vasodilatory component of action of norepinephrine, but not of angiotensin-II. Thus, our initial hypothesis was confirmed - that disruption of the vasodilatory components of various agonists are independent, and that agonist-specific information may prove useful. Next, we employed our new methodology utilizing the rat aorta as our vascular model to test the hypothesis that chronic cocaine administration causes endothelial dysfunction. We first examined the endothelium-dependent vasodilation component of a number of physiologically important vasoconstrictors, and attempted to determine which vasodilatory mediators contributed to the effect. We found the endothelium to have a profound effect on the dose response curve to three important endogenous agonists. These data suggest that under conditions of endothelial dysfunction exaggerated vasoconstriction could occur, even within normal plasma concentration ranges of these vasoconstrictors, resulting in elevated blood pressure and further damage to the endothelium over time. No endothelial dysfunction was observed with this treatment paradigm, using our methodology or the standard…
Advisors/Committee Members: Tallarida, Ronald J.;, Ruggieri, Michael R., Heckman, James L., Parry, Tom Jay, Raffa, Robert B., McGonigle, Paul;.
Subjects/Keywords: Pharmacology;
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APA (6th Edition):
Lamarre, N. S. (2013). Utilizing novel dose equivalence methodologies to examine cocaine's effects on the vasculature. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,221180
Chicago Manual of Style (16th Edition):
Lamarre, Neil Stanley. “Utilizing novel dose equivalence methodologies to examine cocaine's effects on the vasculature.” 2013. Doctoral Dissertation, Temple University. Accessed January 24, 2020.
http://digital.library.temple.edu/u?/p245801coll10,221180.
MLA Handbook (7th Edition):
Lamarre, Neil Stanley. “Utilizing novel dose equivalence methodologies to examine cocaine's effects on the vasculature.” 2013. Web. 24 Jan 2020.
Vancouver:
Lamarre NS. Utilizing novel dose equivalence methodologies to examine cocaine's effects on the vasculature. [Internet] [Doctoral dissertation]. Temple University; 2013. [cited 2020 Jan 24].
Available from: http://digital.library.temple.edu/u?/p245801coll10,221180.
Council of Science Editors:
Lamarre NS. Utilizing novel dose equivalence methodologies to examine cocaine's effects on the vasculature. [Doctoral Dissertation]. Temple University; 2013. Available from: http://digital.library.temple.edu/u?/p245801coll10,221180
Temple University
27.
Kim, Jae Kyun.
CXCL12/CXCR4 signaling in mesocorticolimbic reward pathways: relevance to cocaine reinforcement and relapse.
Degree: PhD, 2016, Temple University
URL: http://digital.library.temple.edu/u?/p245801coll10,399036
► Pharmacology
The role of chemokines as chemotactic cytokines and their functions in the immune system and related pathologies are well defined. Recently, strong evidence supporting…
(more)
▼ Pharmacology
The role of chemokines as chemotactic cytokines and their functions in the immune system and related pathologies are well defined. Recently, strong evidence supporting the hypothesis that chemokines can act as modulators of neuronal activity and influence neurotransmission has been reported. The chemokine CXCL12 is constitutively expressed in adult brain and expression of CXCL12 and its cognate receptor CXCR4 have been reported in regions of rat brain that construct dopamine (DA) and glutamate (GLU) pathways such as ventral tegmental area (VTA), substantia nigra (SN), and nucleus accumbens (NAc). In the central nervous system (CNS), activation of CXCR4 on dopaminergic neurons and astrocytes initiate cascade of events that leads to DA and GLU release and influence synaptic transmission. In vivo, intracerebroventricular (ICV) CXCL12 has been shown to potentiate cocaine-induced locomotor activity. Based on these evidences, the studies, as outlined in this dissertation, aimed to expand understanding of how CXCL12/CXCR4 interaction can affect cocaine-induced behavior and reinforcement, with special focus on mechanisms involving GLU. We first evaluated involvement of CXCR4 activation by CXCL12 on cocaine-induced locomotor activity using a selective CXCR4 antagonist AMD3100. Results demonstrated that AMD3100 (5, 10 mg/kg, IP) pretreatment dose-dependently attenuated cocaine-induced locomotor activity without affecting the baseline activity. Thereafter, effects of AMD3100 on cocaine’s reinforcing efficacy were tested using a biased conditioned place preference (CPP) paradigm. In all CPP experiments, saline pretreated controls established a significant preference for the cocaine-paired context following four pairings with cocaine (10 mg/kg, IP). Rats pretreated with 2.5 and 5 mg/kg AMD3100 prior to each pairing session showed significantly lower preference for the cocaine-paired side, whereas rats pretreated with 1 mg/kg AMD3100 showed similar preference for the cocaine-paired side as the saline controls when tested in the absence of the drug. Rats pretreated with AMD3100 (5 mg/kg, IP) just once prior to testing showed significantly lower preference for the cocaine-paired side. These results demonstrate that CXCR4 antagonism reduces development and expression of cocaine-induced CPP. Intravenous cocaine self-administration (SA) was performed to examine the effects of AMD3100 on the acquisition of cocaine-taking behavior and reinstatement to cocaine-seeking. Acquisition of cocaine SA was studied using three doses of cocaine (0.375, 0.5, 0.75 mg/kg/infusion) on a fixed-ratio 1 (FR-1) schedule of reinforcement. Two doses of AMD3100 (5, 10 mg/kg, IP) were tested. In all SA experiments, saline pretreated controls readily acquired cocaine self-administration. The lower and higher AMD3100 decreased the number of reinforcers earned during the two hour sessions compared to saline controls when tested against acquisition of 0.375 and 0.5 mg/kg/infusion cocaine. However, when tested against the 0.75 mg/kg/infusion…
Advisors/Committee Members: Rawls, Scott M;, Ashby, Barrie, Unterwald, Ellen M, Eisenstein, Toby K, Ramirez, Servio H, Walker, Ellen A;.
Subjects/Keywords: Pharmacology;
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APA ·
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APA (6th Edition):
Kim, J. K. (2016). CXCL12/CXCR4 signaling in mesocorticolimbic reward pathways: relevance to cocaine reinforcement and relapse. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,399036
Chicago Manual of Style (16th Edition):
Kim, Jae Kyun. “CXCL12/CXCR4 signaling in mesocorticolimbic reward pathways: relevance to cocaine reinforcement and relapse.” 2016. Doctoral Dissertation, Temple University. Accessed January 24, 2020.
http://digital.library.temple.edu/u?/p245801coll10,399036.
MLA Handbook (7th Edition):
Kim, Jae Kyun. “CXCL12/CXCR4 signaling in mesocorticolimbic reward pathways: relevance to cocaine reinforcement and relapse.” 2016. Web. 24 Jan 2020.
Vancouver:
Kim JK. CXCL12/CXCR4 signaling in mesocorticolimbic reward pathways: relevance to cocaine reinforcement and relapse. [Internet] [Doctoral dissertation]. Temple University; 2016. [cited 2020 Jan 24].
Available from: http://digital.library.temple.edu/u?/p245801coll10,399036.
Council of Science Editors:
Kim JK. CXCL12/CXCR4 signaling in mesocorticolimbic reward pathways: relevance to cocaine reinforcement and relapse. [Doctoral Dissertation]. Temple University; 2016. Available from: http://digital.library.temple.edu/u?/p245801coll10,399036
University of Minnesota
28.
Gu, Lidan.
Delay discounting as a measure of impulsivity.
Degree: PhD, Educational Psychology, 2012, University of Minnesota
URL: http://purl.umn.edu/137024
► Delay discounting as a behavioral measure of impulsivity has been widely used in neuroeconomy, psychopathology, clinical neuroscience, and drug addiction studies. Previous psychological studies have…
(more)
▼ Delay discounting as a behavioral measure of impulsivity has been widely used in neuroeconomy, psychopathology, clinical neuroscience, and drug addiction studies. Previous psychological studies have suggested that: 1) a hyperbolic function best describes the decision behaviors of humans and other animals; 2) drug users tend to have higher delay discounting rates than controls; and 3) the associations between delay discounting rate and personality measures of delay discounting are inconsistent across studies. However, neuroimaging studies have often observed two neural systems involved in delay discounting, and a number of neural models have been proposed to describe delay discounting. The studies reported in this dissertation investigated delay discounting as a behavioral measure of impulsivity when considering the neural models.
In Chapter 1, delay discounting and its designs, task procedures, analysis models, reliability, and validity are reviewed. Based on previous studies, the delay discounting rate is influenced by the design of delay discounting tasks such as reward magnitude; the delay discounting rate reliably differentiates drug users from controls; and its reliability is high within a normal population but is relatively lower in clinical populations. In Chapter 2, the current studies are introduced.
In Chapter 3, three neural model fitting equations are compared with the standard exponential model and hyperbolic model. The studies suggest the saturating-hyperbolic model fits better than the standard models when the reward magnitude is low (10). The superiority of the saturating-hyperbolic model is even more robust when clinical populations are involved. However, the saturating-hyperbolic model does not fit the empirical data better than the standard models when the reward magnitude is high (1000).
In Chapter 4, cocaine users are compared with matched controls and with individuals with binge eating disorder on their delay discounting rates; the parameters are analyzed by the saturating-hyperbolic function. The results show that cocaine users do not have significantly higher delay discounting rates; rather, they have significantly higher saturation indices, indicating the observed decision making bias in cocaine users is associated with the decision factor related to reward utility instead of the decision factor related to time utility. Furthermore, the findings suggest the observed decision making bias in cocaine users is not associated with binge eating disorder, indicating the decision preference is likely to be specific to drug users.
In Chapter 5, a personality measure based on the construct of time preference (the Time Preference Scale) is introduced. Its psychometric properties and its association with delay discounting and with the Barrat Impulsiveness Scale are investigated. The Time Preference Scale appears to have high reliability and validity. The latent trait of time preference is significantly associated with delay discounting rate. In addition, time preference is better than the overall…
Subjects/Keywords: Cocaine addiction; Decision making; Delay discounting; Impulsivity
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APA (6th Edition):
Gu, L. (2012). Delay discounting as a measure of impulsivity. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/137024
Chicago Manual of Style (16th Edition):
Gu, Lidan. “Delay discounting as a measure of impulsivity.” 2012. Doctoral Dissertation, University of Minnesota. Accessed January 24, 2020.
http://purl.umn.edu/137024.
MLA Handbook (7th Edition):
Gu, Lidan. “Delay discounting as a measure of impulsivity.” 2012. Web. 24 Jan 2020.
Vancouver:
Gu L. Delay discounting as a measure of impulsivity. [Internet] [Doctoral dissertation]. University of Minnesota; 2012. [cited 2020 Jan 24].
Available from: http://purl.umn.edu/137024.
Council of Science Editors:
Gu L. Delay discounting as a measure of impulsivity. [Doctoral Dissertation]. University of Minnesota; 2012. Available from: http://purl.umn.edu/137024
University of Minnesota
29.
Ingebretson, Anna.
Characterizing cellular mechanisms of cocaine-evoked synaptic plasticity in the nucleus accumbens.
Degree: PhD, Neuroscience, 2017, University of Minnesota
URL: http://hdl.handle.net/11299/194598
► Repeated exposure to drugs of abuse alters the structure and function of neural circuits mediating reward, generating maladaptive plasticity in circuits critical for motivated behavior.…
(more)
▼ Repeated exposure to drugs of abuse alters the structure and function of neural circuits mediating reward, generating maladaptive plasticity in circuits critical for motivated behavior. Within mesocorticolimbic dopamine circuitry, repeated exposure to cocaine induces progressive alterations in AMPAR-mediated glutamatergic synaptic transmission. During abstinence from cocaine treatment, AMPAR signaling is potentiated at synapses on nucleus accumbens (NAc) medium spiny neurons (MSNs), promoting a state of heightened synaptic excitability. Re-exposure to cocaine during abstinence, however, reverses and depotentiates enhanced AMPAR signaling, demonstrating that cocaine bidirectionally alters excitatory synaptic transmission in the NAc. Understanding the neurobiological mechanisms underlying drug-induced synaptic adaptations in the NAc could provide targets for developing strategies to reverse or offset maladaptive processes driving long-lasting vulnerability to relapse. However, the detailed cellular signaling mechanisms mediating cocaine-evoked plasticity have not been well-characterized. Using pharmacological approaches in combination with patch-clamp recordings in the NAc, we investigated the role of candidate signaling factors that mediate adaptive synaptic plasticity in the striatum. Among these, activation of group I metabotropic receptors (mGluR1/5) play a prominent role in synaptic depression at excitatory synapses, and furthermore are implicated in models of relapse to drug-seeking. Consistent with this, we found that activation of mGluR5 is necessary for cocaine-induced depotentiation of AMPAR signaling in the NAc. Downstream of mGluR1/5 receptors, mobilization of endogenous cannabinoids (eCBs) is an important factor modulating excitatory synaptic strength. Dopamine receptors in the striatum also broadly modulate synaptic transmission at glutamatergic terminals on MSNs, and are critically engaged by drugs of abuse. Both dopamine and eCB signaling were necessary factors in the induction of cocaine-induced synaptic plasticity in the NAc, suggesting that these neuromodulators may modify the responsiveness of MSNs to alterations in glutamatergic input induced by cocaine. Finally, we examined plasticity at synapses on specific MSN cell subpopulations, demonstrating that specific dopamine receptors on distinct cell types promote specific modifications in AMPAR synaptic function following cocaine experience. These neuromodulatory signaling mechanisms may serve to gate the induction of plasticity at glutamatergic afferents on NAc MSNs by converging on common factors that control the sensitivity of MSNs to excitatory input, ultimately driving addiction-related behavior.
Subjects/Keywords: Cocaine; Nucleus accumbens; Striatum; Synaptic plasticity
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APA (6th Edition):
Ingebretson, A. (2017). Characterizing cellular mechanisms of cocaine-evoked synaptic plasticity in the nucleus accumbens. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/194598
Chicago Manual of Style (16th Edition):
Ingebretson, Anna. “Characterizing cellular mechanisms of cocaine-evoked synaptic plasticity in the nucleus accumbens.” 2017. Doctoral Dissertation, University of Minnesota. Accessed January 24, 2020.
http://hdl.handle.net/11299/194598.
MLA Handbook (7th Edition):
Ingebretson, Anna. “Characterizing cellular mechanisms of cocaine-evoked synaptic plasticity in the nucleus accumbens.” 2017. Web. 24 Jan 2020.
Vancouver:
Ingebretson A. Characterizing cellular mechanisms of cocaine-evoked synaptic plasticity in the nucleus accumbens. [Internet] [Doctoral dissertation]. University of Minnesota; 2017. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/11299/194598.
Council of Science Editors:
Ingebretson A. Characterizing cellular mechanisms of cocaine-evoked synaptic plasticity in the nucleus accumbens. [Doctoral Dissertation]. University of Minnesota; 2017. Available from: http://hdl.handle.net/11299/194598
University of Illinois – Urbana-Champaign
30.
Mustroph, Martina.
Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice.
Degree: PhD, 0323, 2015, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/72960
► Treatments for drug abuse and addiction remain largely ineffective. Recent studies in both the human and rodent literature suggest that exercise-based interventions for drug addiction…
(more)
▼ Treatments for drug abuse and addiction remain largely ineffective. Recent studies in both the human and rodent literature suggest that exercise-based interventions for drug addiction have positive outcomes. Exercise has many effects in the brain. The mechanism by which exercise achieves positive outcomes relevant to drug abuse and addiction is not known. One idea is that exercise extends plasticity to the brain that helps to weaken drug-context associations underlying drug abuse and addiction. It is known that exercise increases hippocampal neurogenesis. However, recently, conflicting reports have been published showing hippocampal neurogenesis to either be involved in or not contributory to learning and memory, and so the role of hippocampal neurogenesis in weakening learned drug-context associations remains unclear. The goal of my dissertation is to identify and evaluate select potential mechanisms causally related to accelerated extinction of conditioned place preference (CPP) for
cocaine from exercise in male C57BL/6J mice. Since the conditioned place preference paradigm represents the major behavioral assay I employ in the proposed experiments, Chapter 1 presents a review of the relevant conditioned place preference literature. Chapter 2 examines the hypothesis that timing of exercise relative to conditioning has opposing effects on
cocaine CPP in male C57BL/6J mice, and that exercise induces hippocampal neurogenesis. The main findings were that wheel running accelerated extinction of CPP when running occurred entirely after drug conditioning, whereas running delayed extinction when administered before conditioning, and that running approximately doubled adult hippocampal neurogenesis. Chapter 3 assesses the relative contribution of running versus enrichment to the neurogenic and pro-cognitive effects of an enriched environment in male C57BL/6J mice. The main finding was that an enriched environment devoid of running wheels did not significantly up-regulate hippocampal neurogenesis or improve behavioral performance on a spatial learning task, although running approximately doubled adult hippocampal neurogenesis. The finding that only running bestowed significant neurogenic and behavioral effects leaves open the possibility environmental enrichment promotes other types of neural plasticity that may make it a suitable substitute for running as an intervention in other domains. Therefore, Chapter 4 investigates the possibility that environmental enrichment, like running, can accelerate extinction of CPP. Results suggest that environmental enrichment does not effectively accelerate extinction of CPP, nor does it significantly increase hippocampal neurogenesis. Chapter 5 directly tests the hypothesis that new neurons from running are necessary for accelerated extinction of
cocaine CPP from running. Chapter 6 attempts to answer the question of whether there are neuropeptides that are differentially induced in runners versus sedentary C57BL/6J mice in the amygdala and hippocampus after exposure to a drug-associated…
Advisors/Committee Members: Rhodes, Justin S. (advisor), Rhodes, Justin S. (Committee Chair), Sweedler, Jonathan V. (committee member), Ceman, Stephanie S. (committee member), Gulley, Joshua M. (committee member).
Subjects/Keywords: cocaine; conditioned place preference; exercise; hippocampal neurogenesis
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APA (6th Edition):
Mustroph, M. (2015). Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/72960
Chicago Manual of Style (16th Edition):
Mustroph, Martina. “Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice.” 2015. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 24, 2020.
http://hdl.handle.net/2142/72960.
MLA Handbook (7th Edition):
Mustroph, Martina. “Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice.” 2015. Web. 24 Jan 2020.
Vancouver:
Mustroph M. Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2015. [cited 2020 Jan 24].
Available from: http://hdl.handle.net/2142/72960.
Council of Science Editors:
Mustroph M. Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2015. Available from: http://hdl.handle.net/2142/72960
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Open Access Theses and Dissertations
