{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/11249"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/11249","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Role of the Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) in Cocaine Cue Reactivity","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Jackson, Sarah"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Neuroscience (Doctoral)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Cunningham, Kathryn A"],"committee_chairs":[],"committee_members":["Hommel, Jonathan D","Watson, Cheryl S","Moeller, F Gerard","Gilbertson, Scott R"],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:51:06Z","subjects":["cocaine cue reactivity","serotonin 5-HT2C receptor"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152.3/11249","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Cunningham, Kathryn A"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Hommel, Jonathan D","Watson, Cheryl S","Moeller, F Gerard","Gilbertson, Scott R"]},{"key":"dc:creator","label":"Author","values":["Jackson, Sarah"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2020-11-17T20:55:13Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2020-11-17T20:55:13Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Neuroscience (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cocaine cue reactivity","serotonin 5-HT2C receptor"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.3/11249"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Role of the Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) in Cocaine Cue Reactivity"]}]}],"canonical_facts":{"dc:contributor.advisor":["Cunningham, Kathryn A"],"dc:contributor.committeemember":["Hommel, Jonathan D","Watson, Cheryl S","Moeller, F Gerard","Gilbertson, Scott R"],"dc:creator":["Jackson, Sarah"],"dc:date.accessioned":["2020-11-17T20:55:13Z"],"dc:date.available":["2020-11-17T20:55:13Z"],"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/2152.3/11249"],"dc:subject":["cocaine cue reactivity","serotonin 5-HT2C receptor"],"dc:title":["Role of the Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) in Cocaine Cue Reactivity"],"dc:type":["Thesis"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Neuroscience (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:51:06Z"}