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Chemogenetic manipulating activity of aIC neurons, especially aIC glutamatergic neurons, bidirectionally regulated compulsive cocaine intake. Furthermore, the aIC received inputs from the orbitofrontal cortex (OFC), and the OFC-aIC circuit was enhanced in rats with compulsive cocaine use. Suppression of the OFC-aIC circuit switched rats from punishment resistance to sensitivity, while potentiation of this circuit increased compulsive cocaine use. In conclusion, our results found that aIC glutamatergic neurons and the OFC-aIC circuit gated the shift from controlled to compulsive cocaine use, which could serve as potential therapeutic targets for drug addiction.<\/jats:p>","DOI":"10.1126\/sciadv.abq5745","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T13:58:15Z","timestamp":1671803895000},"source":"Crossref","is-referenced-by-count":32,"title":["An orbitofrontal cortex\u2013anterior insular cortex circuit gates compulsive cocaine use"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8613-0137","authenticated-orcid":true,"given":"Yang","family":"Chen","sequence":"first","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China."},{"name":"Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-529X","authenticated-orcid":true,"given":"Guibin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; 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