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However, the role of oligodendrocytes in stress\u2010induced cocaine relapses remains unclear. In the present study, we investigated the role of the oligodendrocyte\u2010abundant molecule crystallin alpha B (CRYAB) in cocaine\u2010induced conditioned place preference (CPP) relapsed by restraint stress. RNA sequencing (RNA\u2010seq) was performed to identify oligodendrocytes and stress\u2010associated molecules in the nucleus accumbens (NAcc) of both drug users and cocaine\u2010treated animals. Further, we studied which cell subtypes in the brain express CRYAB. The effects of stress hormones and cocaine on CRYAB expression were evaluated in\u00a0vitro in human oligodendrocytes. CRYAB is upregulated in the NAcc of both cocaine\u2010treated animals and drug users. CRYAB levels in the NAcc of mice increased during CPP development but decreased following stress\u2010induced relapse. Interestingly, CRYAB is expressed in oligodendrocytes in the NAcc of mice. Extracellular CRYAB levels are regulated by cocaine and stress hormone treatments in oligodendrocyte cultures. Dopamine levels in the NAcc and CPP development of CPP are significantly increased by cocaine in CRYAB knockout (KO) mice. Further, we demonstrated that CRYAB binds to the excitatory amino acid transporter 2 (EAAT2) in the NAcc of mice treated with cocaine. We suggest that oligodendrocyte\u2010derived CRYAB regulates dopamine neurotransmission and stress\u2010evoked cocaine reward behaviour via the modulation of EAAT2 in the NAcc.<\/jats:p>","DOI":"10.1111\/adb.70028","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T11:35:26Z","timestamp":1742211326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Crystallin Alpha B Inhibits Cocaine\u2010Induced Conditioned Place Preference via the Modulation of Dopaminergic Neurotransmission"],"prefix":"10.1111","volume":"30","author":[{"given":"Sun\u00a0Mi","family":"Gu","sequence":"first","affiliation":[{"name":"College of Pharmacy Chungbuk National University  Cheongju Chungcheongbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daejin","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University  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