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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 demonstrate in mouse NAcSh slices that D1R agonists increase astrocytic Ca\n                  <jats:sup>2+<\/jats:sup>\n                  activity, an effect that is attenuated by astrocyte-specific D1R knockdown. Furthermore, selective knockdown of astrocytic D1R in the NAcSh prior to cocaine self-administration inhibits cocaine-induced generation of silent synapses, therefore hampering the associated remodeling of NAcSh circuits. Behaviorally, knockdown of NAcSh astrocytic D1R expedites the extinction of cocaine seeking and reduces cue-induced reinstatement. These results identify astrocytic D1R as a fundamental component of NAcSh dopamine signaling during cocaine experience that remodels synaptic connections and neural networks underlying drug seeking and relapse.\n                <\/jats:p>","DOI":"10.64898\/2026.05.13.724947","type":"posted-content","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:00:21Z","timestamp":1779116421000},"source":"Crossref","is-referenced-by-count":0,"title":["Astrocytic D1 Dopamine-Signaling Regulates Synaptic Remodeling and Cocaine Seeking"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8486-7477","authenticated-orcid":false,"given":"Shi","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qize","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander K.","family":"Zinsmaier","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","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, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiguang","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gouri","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, California, USA"}],"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, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver M.","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Psychiatry and Psychotherapy, University Medical Center G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052105551240000_2026.05.13.724947v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.39"},{"key":"2026052105551240000_2026.05.13.724947v1.2","doi-asserted-by":"crossref","unstructured":"Wright WJ , and Dong Y . 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