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This shift is paralleled by drug\u2010induced (including cocaine) dopamine transporter (DAT) alterations originating in the ventral striatum that spread eventually to encompass the aDLS. Having recently shown that heroin self\u2010administration results in a pan\u2010striatal reduction in astrocytic DAT that precedes the development of aDLS dopamine\u2010dependent incentive heroin\u2010seeking habits, we tested the hypothesis that similar adaptations occur following cocaine exposure. We compared DAT protein levels in whole tissue homogenates, and in astrocytes cultured from ventral and dorsal striatal territories of drug\u2010na\u00efve male Sprague\u2013Dawley rats to those of rats with a history of cocaine taking or an aDLS dopamine\u2010dependent incentive cocaine\u2010seeking habit. Cocaine exposure resulted in a decrease in whole tissue and astrocytic DAT across all territories of the striatum. We further demonstrated that compulsive (i.e., punishment\u2010resistant) incentive cocaine\u2010seeking habits were associated with a reduction in DAT mRNA levels in the Nac shell, but not the Nac core\u2010aDLS incentive habit system. Together with the recent evidence of heroin\u2010induced downregulation of striatal astrocytic DAT, these findings suggest that alterations in astrocytic DAT may represent a common mechanism underlying the development of compulsive incentive drug\u2010seeking habits across drug classes.<\/jats:p>","DOI":"10.1111\/ejn.70054","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:22:06Z","timestamp":1741911726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Incentive Cocaine\u2010Seeking Habits and Their Compulsive Manifestation Emerge After a Downregulation of the Dopamine Transporter in Astrocytes Across Functional Domains of the Striatum"],"prefix":"10.1111","volume":"61","author":[{"given":"Maxime","family":"Fouyssac","sequence":"first","affiliation":[{"name":"Department of Psychology University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"Hynes","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aude","family":"Belin\u2010Rauscent","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhaval\u00a0D.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-372X","authenticated-orcid":false,"given":"David","family":"Belin","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106362"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23963"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.01.025"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199711)27:3<230::AID-SYN8>3.0.CO;2-E"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.12.013"},{"key":"e_1_2_10_8_1","unstructured":"Chernoff C. 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