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Leveraging advancements in neuroproteomics, we undertook a proteomic analysis that spanned membrane, cytosolic, nuclear, and chromatin compartments of the NAc in a mouse model. The results unveiled immediate and sustained proteomic modifications after cocaine exposure and during prolonged withdrawal. We identified congruent protein regulatory patterns during initial cocaine exposure and reexposure after withdrawal, which contrasted with distinct patterns during withdrawal. Pronounced proteomic shifts within the membrane compartment indicated adaptive and long-lasting molecular responses prompted by cocaine withdrawal. In addition, we identified potential protein translocation events between soluble-nuclear and chromatin-bound compartments, thus providing insight into intracellular protein dynamics after cocaine exposure. Together, our findings illuminate the intricate proteomic landscape that is altered in the NAc by cocaine use and provide a dataset for future research toward potential therapeutics.<\/jats:p>","DOI":"10.1126\/scisignal.adl4738","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T17:58:45Z","timestamp":1713290325000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens"],"prefix":"10.1126","volume":"17","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 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-2290","authenticated-orcid":true,"given":"Lucas","family":"Sosnick","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5838-0504","authenticated-orcid":true,"given":"Ashik","family":"Gurung","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9073-6641","authenticated-orcid":true,"given":"Simone","family":"Sidoli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Einstein College of Medicine, New York, NY 10461, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7905-2000","authenticated-orcid":true,"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, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.113009"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2014.11.002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz6596"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2017.08.031"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax1532"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-019-05074-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.11.982"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.11.973"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.4.687"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.11.967"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","unstructured":"F. 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