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We link prolonged withdrawal from cocaine to the depletion of the histone variant H2A.Z, coupled with increased genome accessibility and latent priming of gene transcription, in D1 dopamine receptor\u2013expressing medium spiny neurons (D1 MSNs) that relate to aberrant gene expression upon drug relapse. The histone chaperone ANP32E removes H2A.Z from chromatin, and we demonstrate that D1 MSN\u2013selective\n                    <jats:italic>Anp32e<\/jats:italic>\n                    knockdown prevents cocaine-induced H2A.Z depletion and blocks cocaine\u2019s rewarding actions. By contrast, very different effects of cocaine exposure, withdrawal, and relapse were found for D2 MSNs. These findings establish histone variant exchange as an important mechanism and clinical target engaged by drugs of abuse to corrupt brain function and behavior.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ado3514","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T13:58:42Z","timestamp":1728050322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":20,"title":["Cell type\u2013specific epigenetic priming of gene expression in nucleus accumbens by cocaine"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2052-1578","authenticated-orcid":true,"given":"Philipp","family":"Mews","sequence":"first","affiliation":[{"name":"Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yentl","family":"Van der 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