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These effects are thought to underlie addictive behaviors. In the ventral tegmental area (VTA), glutamatergic synapses also exhibit long\u2010term depression (LTD), a type of plasticity that weakens synaptic strength. This form of synaptic plasticity is induced by low\u2010frequency stimulation and mediated by endocannabinoid (eCB) signaling, which also modulates addictive behaviors. However, it remains unknown whether eCB\u2010LTD in the VTA could be altered by cocaine use. Therefore, the goal of the present study was to examine the impact of cocaine self\u2010administration on eCB\u2010LTD of glutamatergic synapses onto VTA dopaminergic (DA) neurons. To that end, male rats underwent cocaine (0.75\u00a0mg\/kg\/infusion) or saline self\u2010administration under the fixed ratio 1 schedule for 6\u20139\u00a0days. One day after the last self\u2010administration session, the magnitude of eCB\u2010LTD was examined using ex vivo whole\u2010cell recordings of putative VTA DA neurons from na\u00efve rats and rats with saline or cocaine self\u2010administration. The results revealed that cocaine self\u2010administration abolished eCB\u2010LTD. The cocaine\u2010induced blockade of eCB\u2010LTD in the VTA was mediated by an impaired function of presynaptic CB1 receptors. Collectively, these findings indicate that cocaine exposure blunts eCB\u2010mediated synaptic plasticity in midbrain DA neurons. This effect could be one of the cellular mechanisms that mediate, at least in part, addictive behaviors.<\/jats:p>","DOI":"10.1111\/ejn.14980","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T01:41:38Z","timestamp":1600738898000},"page":"4517-4524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cocaine self\u2010administration abolishes endocannabinoid\u2010mediated long\u2010term depression of glutamatergic synapses in the ventral tegmental area"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0316-0600","authenticated-orcid":false,"given":"Ruixiang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn 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