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Here, we investigated the role of neurons which express these receptors (D1\u2010neurons) in the acute locomotor effects of cocaine and the locomotor sensitization observed after a second injection of this drug, using the previously established two\u2010injection protocol of sensitization. We inhibited D1\u2010neurons using double transgenic mice conditionally expressing the inhibitory Gi\u2010coupled designer receptor exclusively activated by designer drugs (Gi\u2010DREADD) in D1\u2010neurons. Chemogenetic inhibition of D1\u2010neurons by a low dose of clozapine (0.1\u2009mg\/kg) decreased the cocaine\u2010induced expression of Fos in striatal neurons. It diminished the basal locomotor activity and acute hyper\u2010locomotion induced by cocaine (20\u2009mg\/kg). Clozapine 0.1\u2009mg\/kg had no effect by itself and did not alter cocaine effects in wild\u2010type mice. Inhibition of D1\u2010neurons during the first cocaine administration prevented the sensitization of the locomotor response in response to a second cocaine administration 10\u2009days later. On Day 11, inhibition of D1\u2010neurons by clozapine stimulation of Gi\u2010DREADD blocked cocaine\u2010induced locomotion including in sensitized mice, whereas on Day 12, in the absence of clozapine and D1\u2010neurons inhibition, all mice displayed a sensitized response to cocaine. These results show that chemogenetic inhibition of D1\u2010neurons decreases spontaneous and cocaine\u2010induced locomotor activity. It prevents sensitization induction and blocks sensitized locomotion in a two\u2010injection protocol of sensitization but does not reverse established sensitization. Our study further supports the central role of D1\u2010neurons in mediating the acute locomotor effects of cocaine and its sensitization.<\/jats:p>","DOI":"10.1111\/ejn.15394","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T09:41:43Z","timestamp":1626514903000},"page":"5327-5340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dopamine D1 receptor\u2010expressing neurons activity is essential for locomotor and sensitizing effects of a single injection of cocaine"],"prefix":"10.1111","volume":"54","author":[{"given":"Yukari","family":"Nakamura","sequence":"first","affiliation":[{"name":"INSERM UMR\u2010S 1270  Paris France"},{"name":"Faculty of Sciences and Engineering Sorbonne University  Paris France"},{"name":"Institut du Fer \u00e0 Moulin  Paris France"},{"name":"Department of Pharmacology Kurume University School of Medicine  Kurume 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