Role of the Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) in Cocaine Cue Reactivity
| dc.contributor.advisor | Cunningham, Kathryn A | |
| dc.contributor.committeeMember | Hommel, Jonathan D | |
| dc.contributor.committeeMember | Watson, Cheryl S | |
| dc.contributor.committeeMember | Moeller, F Gerard | |
| dc.contributor.committeeMember | Gilbertson, Scott R | |
| dc.creator | Jackson, Sarah | |
| dc.date.accessioned | 2020-11-17T20:55:10Z | |
| dc.date.available | 2020-11-17T20:55:10Z | |
| dc.date.created | 2016-05 | |
| dc.date.submitted | May 2016 | |
| dc.date.updated | 2020-11-17T20:55:12Z | |
| dc.description.abstract | Cocaine 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. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/2152.3/11248 | |
| dc.subject | cocaine cue reactivity | |
| dc.subject | serotonin 5-HT2C receptor | |
| dc.title | Role of the Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) in Cocaine Cue Reactivity | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Neuroscience | |
| thesis.degree.grantor | The University of Texas Medical Branch at Galveston | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Neuroscience (Doctoral) |