{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80547"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80547","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Endocannabinoids Regulation of Reward-Predictive Cue Processing","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Leigh, Martin; 0000-0002-8238-2975"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Bass, Caroline","Pharmacology and Toxicology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-10-25T16:05:43Z","date_published":"2019-10-25T16:05:43Z","updated_at":"2026-07-27T19:05:23Z","subjects":["pharmacology"],"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/10477/80547","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bass, Caroline","Pharmacology and Toxicology"]},{"key":"dc:creator","label":"Author","values":["Leigh, Martin; 0000-0002-8238-2975"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-10-25T16:05:43Z","2019","2019-08-09 13:24:56"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmacology"]}]},{"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/10477/80547"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Cannabis sativa is one of the most commonly abused substances worldwide and acts primarily through the endocannabinoid system (ECS). This system, comprising CB1/2 receptors, is endogenously activated by the endocannabinoids (eCB) 2-arachidonyl glycerol (2-AG) and anandamide (AEA). 2-AG and AEA levels are regulated by the degradative enzymes monoacylglycerol lipase (MAGL) and fatty acid hydrolase (FAAH), respectively. While the role of the endocannabinoid system is being explored in multiple behavioral phenomena, the effects of 2-AG to on food intake are inconsistent and understudied. In this study we used a novel MAGL inhibitor, MJN110 to determine if the incentive motivational properties of reward predictive cues are regulated by elevated 2-AG levels. In addition, we employed CB1 (rimonabant) and CB2 (SR144528) antagonists/inverse agonists as well as a FAAH inhibitor (PF3845) to further elucidate which components of the ECS impacts cue processing. We hypothesized antagonizing the CB1 receptor, using the CB1 inverse agonist rimonabant, would block responding to reward predictive incentive cues, while MJN110 would enhance responding. We further tested whether the ventral tegmental area (VTA) and/or Nucleus Accumbens (NAc) is the primary site of action responsible for these effects. Our operant task allowed us to parse the incentive properties of the cues from other aspects of operant responding. Rats were required to nosepoke during an intermittent audio-visual incentive cue (IC) to obtain a 10% sucrose reward. The CB1 receptor antagonist rimonabant was administered in 1, 3, and 6 mg/kg doses (i.p.) 30 min prior to the behavioral task, whereas, MJN110 was administered as 1, 5, and 10 mg/kg doses. For intracranial experiments MJN110 (2µg, 4 µg), PF3845 (4µg), rimonabant (3µg), or SR144528 (3µg) were infused into either the VTA or NAc to affect responding to ICs. Systemic rimonabant decreased the choice to respond in our behavioral task, while increasing the latency to respond to the cue. Systemic MAGL enhanced responding in a variant of the IC task, where the reward was progressively reduced every 15 min in the 1-hr session. Intracranial administration of the agents during this decreasing reward IC task demonstrate that MAGL inhibition increases the incentive motivational properties of the cues, while FAAH inhibition had no effect.Our results suggest that heterogeneous eCBs signaling in the VTA and NAc plays a key role in reward processing for incentivizing cues, which is primarily mediated by 2-AG."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Endocannabinoids Regulation of Reward-Predictive Cue Processing"]}]}],"canonical_facts":{"dc:contributor":["Bass, Caroline","Pharmacology and Toxicology"],"dc:creator":["Leigh, Martin; 0000-0002-8238-2975"],"dc:date":["2019-10-25T16:05:43Z","2019","2019-08-09 13:24:56"],"dc:description":["M.S.","Cannabis sativa is one of the most commonly abused substances worldwide and acts primarily through the endocannabinoid system (ECS). This system, comprising CB1/2 receptors, is endogenously activated by the endocannabinoids (eCB) 2-arachidonyl glycerol (2-AG) and anandamide (AEA). 2-AG and AEA levels are regulated by the degradative enzymes monoacylglycerol lipase (MAGL) and fatty acid hydrolase (FAAH), respectively. While the role of the endocannabinoid system is being explored in multiple behavioral phenomena, the effects of 2-AG to on food intake are inconsistent and understudied. In this study we used a novel MAGL inhibitor, MJN110 to determine if the incentive motivational properties of reward predictive cues are regulated by elevated 2-AG levels. In addition, we employed CB1 (rimonabant) and CB2 (SR144528) antagonists/inverse agonists as well as a FAAH inhibitor (PF3845) to further elucidate which components of the ECS impacts cue processing. We hypothesized antagonizing the CB1 receptor, using the CB1 inverse agonist rimonabant, would block responding to reward predictive incentive cues, while MJN110 would enhance responding. We further tested whether the ventral tegmental area (VTA) and/or Nucleus Accumbens (NAc) is the primary site of action responsible for these effects. Our operant task allowed us to parse the incentive properties of the cues from other aspects of operant responding. Rats were required to nosepoke during an intermittent audio-visual incentive cue (IC) to obtain a 10% sucrose reward. The CB1 receptor antagonist rimonabant was administered in 1, 3, and 6 mg/kg doses (i.p.) 30 min prior to the behavioral task, whereas, MJN110 was administered as 1, 5, and 10 mg/kg doses. For intracranial experiments MJN110 (2µg, 4 µg), PF3845 (4µg), rimonabant (3µg), or SR144528 (3µg) were infused into either the VTA or NAc to affect responding to ICs. Systemic rimonabant decreased the choice to respond in our behavioral task, while increasing the latency to respond to the cue. Systemic MAGL enhanced responding in a variant of the IC task, where the reward was progressively reduced every 15 min in the 1-hr session. Intracranial administration of the agents during this decreasing reward IC task demonstrate that MAGL inhibition increases the incentive motivational properties of the cues, while FAAH inhibition had no effect.Our results suggest that heterogeneous eCBs signaling in the VTA and NAc plays a key role in reward processing for incentivizing cues, which is primarily mediated by 2-AG."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80547"],"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":["pharmacology"],"dc:title":["Endocannabinoids Regulation of Reward-Predictive Cue Processing"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:23Z"}