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dc.contributor.advisorCunningham, Kathryn A
dc.creatorJackson, Sarah
dc.date.accessioned2020-11-17T20:55:10Z
dc.date.available2020-11-17T20:55:10Z
dc.date.created2016-05
dc.date.submittedMay 2016
dc.identifier.urihttps://hdl.handle.net/2152.3/11248
dc.description.abstractCocaine use disorder is a chronic brain disorder characterized by high relapse rates and poor treatment outcomes; one variable known to engender relapse is exposure to environmental and discrete cues previously associated with drug-taking (cue reactivity). Human drug users experience an increase in craving elicited by drug-paired cues over time, and in rodent models, a time-dependent increase in cue reactivity (‘incubation”) is observed during forced abstinence from drug self-administration. Neuroplasticity in the mesocorticolimbic neurocircuitry mediates the incubation of cue reactivity, and a greater understanding of the mechanisms underlying incubation phenomena is needed to improve treatment outcomes and extend abstinence. Serotonin (5-HT) neurotransmitter systems play an important role in the behavioral effects of cocaine particularly through the 5-HT2C receptor (5-HT2CR), however, the involvement of this system in incubation of cue reactivity during abstinence from cocaine self-administration has not been investigated. The 5-HT2CR is expressed throughout reward neurocircuitry, but exploration of the region-dependent role of 5-HT2CR function to modulate cocaine-related behaviors, including cue reactivity, has been limited. The present studies aimed to explore the 5-HT2CR localized to nodes of the mesocorticolimbic pathway as a potential neuroregulator of cue reactivity assessed during forced abstinence from cocaine self-administration. Prolonged vs. early forced abstinence from cocaine self-administration was associated with elevated cue reactivity, a lower potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, and an altered subcellular distribution profile of the 5-HT2CR in the medial prefrontal cortex. Levels of cue reactivity and 5-HT2CR protein expression levels within specific nodes (medial prefrontal cortex, ventral tegmental area) of the mesocorticoaccumbens pathway were inversely correlated. A definitive role for the 5-HT2CR in the VTA as a driver of cocaine-related behaviors could not be determined in the present study due to technical limitations in virally-mediated gene transfer experiments. Collectively, these studies illuminate the 5-HT2CR as a potential contributor to the incubation of cue reactivity associated with abstinence from cocaine self-administration. These data shed new light on the involvement of pathway-specific regulation of the 5-HT2CR in a key phenotype associated with relapse suggest new pharmacotherapeutic strategies to curb cue reactivity and prevent relapse to cocaine.
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dc.subjectcocaine cue reactivity
dc.subjectserotonin 5-HT2C receptor
dc.titleRole of the Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) in Cocaine Cue Reactivity
dc.typeThesis
dc.date.updated2020-11-17T20:55:12Z
dc.type.materialtext
thesis.degree.nameNeuroscience (Doctoral)
thesis.degree.levelDoctoral
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.departmentNeuroscience
dc.contributor.committeeMemberHommel, Jonathan D
dc.contributor.committeeMemberWatson, Cheryl S
dc.contributor.committeeMemberMoeller, F Gerard
dc.contributor.committeeMemberGilbertson, Scott R


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