{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:39:22Z","timestamp":1792687162174,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Drug Abuse","award":["DA014133"],"award-info":[{"award-number":["DA014133"]}]},{"name":"National Institute on Drug Abuse","award":["DA040620"],"award-info":[{"award-number":["DA040620"]}]},{"name":"National Institute on Drug Abuse","award":["DA023206"],"award-info":[{"award-number":["DA023206"]}]},{"name":"National Institute on Drug Abuse","award":["DA060808"],"award-info":[{"award-number":["DA060808"]}]},{"name":"National Institute of Mental Health","award":["MH131717"],"award-info":[{"award-number":["MH131717"]}]},{"name":"National Institute on Drug Abuse","award":["U01DA058278"],"award-info":[{"award-number":["U01DA058278"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>D1-type receptor (D1R)-mediated dopaminergic signaling within the nucleus accumbens shell \n(NAcSh) is essential for forming adaptive circuit changes that embed persistent memories associated with drug seeking and craving. While D1R is expressed in both NAcSh neurons and astrocytes, the specific contribution of astrocytic D1R to drug-related circuit plasticity remains poorly understood. Here, we demonstrated in mouse NAcSh slices that D1R agonists increased astrocytic Ca2+ activity, an effect that was attenuated by astrocyte-specific D1R knockdown. Furthermore, selective knockdown of astrocytic D1R in the NAcSh prior to cocaine self-administration inhibited cocaine-induced generation of silent synapses, thereby hampering the associated remodeling of NAcSh circuits. Behaviorally, knockdown of NAcSh astrocytic D1R expedited the extinction of cocaine seeking and reduced cue-induced reinstatement. These results identified astrocytic D1R as a fundamental component of NAcSh dopamine signaling during cocaine experience that remodeled synaptic connections and neural networks underlying drug seeking and relapse.<\/jats:p>","DOI":"10.1172\/jci206794","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:27Z","timestamp":1792684827000},"source":"Crossref","is-referenced-by-count":0,"title":["Dopamine signaling via astrocytic D1 receptors regulates nucleus accumbens synaptic remodeling and cocaine seeking"],"prefix":"10.1172","author":[{"given":"Shi","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qize","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of pittburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander K.","family":"Zinsmaier","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma R.","family":"Huguet","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengsong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiguang","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gouri","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Nestler","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver M.","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,22]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/206794\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:29Z","timestamp":1792684829000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/206794"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"alternative-id":["10.1172\/JCI206794"],"URL":"https:\/\/doi.org\/10.1172\/jci206794","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]}}}