{"doi":"10.1111/ejn.14980","title":"Cocaine self‐administration abolishes endocannabinoid‐mediated long‐term depression of glutamatergic synapses in the ventral tegmental area","abstract":"Drugs of abuse, including cocaine, alter the mechanisms underpinning synaptic plasticity, including long-term potentiation of glutamatergic synapses in the mesolimbic system. These effects are thought to underlie addictive behaviors. In the ventral tegmental area (VTA), glutamatergic synapses also exhibit long-term depression (LTD), a type of plasticity that weakens synaptic strength. This form of synaptic plasticity is induced by low-frequency stimulation and mediated by endocannabinoid (eCB) signaling, which also modulates addictive behaviors. However, it remains unknown whether eCB-LTD in the VTA could be altered by cocaine use. Therefore, the goal of the present study was to examine the impact of cocaine self-administration on eCB-LTD of glutamatergic synapses onto VTA dopaminergic (DA) neurons. To that end, male rats underwent cocaine (0.75 mg/kg/infusion) or saline self-administration under the fixed ratio 1 schedule for 6-9 days. One day after the last self-administration session, the magnitude of eCB-LTD was examined using ex vivo whole-cell recordings of putative VTA DA neurons from naïve rats and rats with saline or cocaine self-administration. The results revealed that cocaine self-administration abolished eCB-LTD. The cocaine-induced blockade of eCB-LTD in the VTA was mediated by an impaired function of presynaptic CB1 receptors. Collectively, these findings indicate that cocaine exposure blunts eCB-mediated synaptic plasticity in midbrain DA neurons. This effect could be one of the cellular mechanisms that mediate, at least in part, addictive behaviors.","journal":"European Journal of Neuroscience","year":2020,"id":84693,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":328285,"name":"Kathryn A. Hausknecht","orcid":"0000-0003-2748-364X","position":1,"is_corresponding":false},{"id":434130,"name":"Amy M. Gancarz","orcid":"0000-0002-3231-9732","position":2,"is_corresponding":false},{"id":434131,"name":"Saida Oubraim","orcid":"0000-0003-4930-2133","position":3,"is_corresponding":false},{"id":328288,"name":"Roh‐Yu Shen","orcid":"0000-0002-0421-3260","position":4,"is_corresponding":false},{"id":328287,"name":"Samir Haj‐Dahmane","orcid":"0000-0002-6012-7199","position":5,"is_corresponding":false},{"id":328283,"name":"Ruixiang Wang","orcid":"0000-0003-0316-0600","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T21:55:38.506333Z","pmid":"32959420","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}