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This process involves the dopamine\u2010dependent functional coupling of the anterior dorsolateral striatum (aDLS) with the nucleus accumbens core, but the mechanisms by which this coupling occurs have not been fully elucidated. The striatum is tiled by a syncytium of astrocytes that express the dopamine transporter (DAT), the level of which is altered in individuals with heroin use disorder. Astrocytes are therefore uniquely placed functionally to bridge dopamine\u2010dependent mechanisms across the striatum. Here we tested the hypothesis that exposure to heroin influences the expression of DAT in striatal astrocytes across the striatum before the development of DLS\u2010dependent incentive heroin seeking habits. Using Western\u2010blot, qPCR, and RNAscope\u2122, we measured DAT protein and mRNA levels in whole tissue, culture and in situ astrocytes from striatal territories of rats with a well\u2010established cue\u2010controlled heroin seeking habit and rats trained to respond for heroin or food under continuous reinforcement. Incentive heroin seeking habits were associated with a reduction in DAT protein levels in the anterior aDLS that was preceded by a heroin\u2010induced reduction in DAT mRNA and protein in astrocytes across the striatum. Striatal astrocytes were also shown to be susceptible to direct dopamine\u2010 and opioid\u2010induced downregulation of DAT expression. These results suggest that astrocytes may critically regulate the striatal dopaminergic adaptations that lead to the development of incentive heroin seeking habits.<\/jats:p>","DOI":"10.1111\/ejn.16354","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:55:36Z","timestamp":1713833736000},"page":"2502-2521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pan\u2010striatal reduction in the expression of the astrocytic dopamine transporter precedes the development of dorsolateral striatum dopamine\u2010dependent incentive heroin seeking habits"],"prefix":"10.1111","volume":"59","author":[{"given":"Tristan","family":"Hynes","sequence":"first","affiliation":[{"name":"Department of Psychology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Fouyssac","sequence":"additional","affiliation":[{"name":"Department of 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