{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79810"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79810","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Opiate-Induced Plasticity in the Mesolimbic Dopamine System","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Martin, Jennifer"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Dietz, David","Pharmacology and Toxicology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-26T18:06:17Z","date_published":"2019-07-26T18:06:17Z","updated_at":"2026-07-27T19:05:19Z","subjects":["neurosciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79810","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dietz, David","Pharmacology and Toxicology"]},{"key":"dc:creator","label":"Author","values":["Martin, Jennifer"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-26T18:06:17Z","2019","2019-05-07 15:13:13"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["neurosciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79810"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Substance use disorder is a chronic, relapsing disease that results from cellular maladaptations within discrete regions of the mesolimbic dopamine system, or the ‘reward pathway.’ Two critical regions that are known to be altered by drugs of abuse are the nucleus accumbens (NAc) and the prefrontal cortex (PFC). It is known that heroin abuse, which has been steadily increasing for the past decade, along with subsequent relapse episodes, produces persistent cellular adaptations within distinct cell populations within the NAc and PFC, which lead to the long-lasting behavioral changes underlying the addicted state. To this end, the work in this dissertation represents research aimed at determining critical cellular adaptations, within specialized cells in the NAc and PFC, which can be targeted for the reversal of drug-induced maladaptive behaviors, including relapse and motivation to seek drug rewards. In the first aim, we examined the role of actin dynamics in the NAc, and specifically the actin regulator drebrin, to mediate drug-induced relapse behaviors. It is well established that opiates, such as heroin, produce pronounced decreases in medium spiny neuron (MSN) dendritic spine density in the NAc. Following heroin self-administration, a preclinical model of addiction that recapitulates relapse-like behaviors, we observe a decrease in spine density concomitant with decreased actin stability, which is accompanied by downregulation of the actin-binding protein, drebrin. In an attempt to restore actin stability, we used viral-mediated gene therapy to overexpress drebrin directly in the NAc. We demonstrate that restitution of drebrin levels following heroin self-administration, blunted heroin-induced relapse behaviors and subsequent heroin- induced spine density loss. Further, using pharmacological manipulation, chromatin immunoprecipitation, and RT-PCR, we establish that drebrin expression is negatively, and directly, regulated by chromatin remodeler, HDAC2. Importantly, we show that changes in drebrin occur within a subset of the NAc MSNs. Together, the findings in this dissertation identify key molecular and cellular signatures within the reward pathway, which can be directly targeted for the reduction and reversal of maladaptive drug-associated behaviors."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Opiate-Induced Plasticity in the Mesolimbic Dopamine System"]}]}],"canonical_facts":{"dc:contributor":["Dietz, David","Pharmacology and Toxicology"],"dc:creator":["Martin, Jennifer"],"dc:date":["2019-07-26T18:06:17Z","2019","2019-05-07 15:13:13"],"dc:description":["Ph.D.","Substance use disorder is a chronic, relapsing disease that results from cellular maladaptations within discrete regions of the mesolimbic dopamine system, or the ‘reward pathway.’ Two critical regions that are known to be altered by drugs of abuse are the nucleus accumbens (NAc) and the prefrontal cortex (PFC). It is known that heroin abuse, which has been steadily increasing for the past decade, along with subsequent relapse episodes, produces persistent cellular adaptations within distinct cell populations within the NAc and PFC, which lead to the long-lasting behavioral changes underlying the addicted state. To this end, the work in this dissertation represents research aimed at determining critical cellular adaptations, within specialized cells in the NAc and PFC, which can be targeted for the reversal of drug-induced maladaptive behaviors, including relapse and motivation to seek drug rewards. In the first aim, we examined the role of actin dynamics in the NAc, and specifically the actin regulator drebrin, to mediate drug-induced relapse behaviors. It is well established that opiates, such as heroin, produce pronounced decreases in medium spiny neuron (MSN) dendritic spine density in the NAc. Following heroin self-administration, a preclinical model of addiction that recapitulates relapse-like behaviors, we observe a decrease in spine density concomitant with decreased actin stability, which is accompanied by downregulation of the actin-binding protein, drebrin. In an attempt to restore actin stability, we used viral-mediated gene therapy to overexpress drebrin directly in the NAc. We demonstrate that restitution of drebrin levels following heroin self-administration, blunted heroin-induced relapse behaviors and subsequent heroin- induced spine density loss. Further, using pharmacological manipulation, chromatin immunoprecipitation, and RT-PCR, we establish that drebrin expression is negatively, and directly, regulated by chromatin remodeler, HDAC2. Importantly, we show that changes in drebrin occur within a subset of the NAc MSNs. Together, the findings in this dissertation identify key molecular and cellular signatures within the reward pathway, which can be directly targeted for the reduction and reversal of maladaptive drug-associated behaviors."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79810"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["neurosciences"],"dc:title":["Opiate-Induced Plasticity in the Mesolimbic Dopamine System"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:19Z"}