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Preliminary study suggested that bromodomain\u2010containing protein 4 (BRD4), an epigenetic reader protein, participates in cocaine\u2010induced reward and neuroplasticity. However, the exact role of BRD4 in cocaine addiction, particularly cocaine relapse, remains elusive. In this study, we found that BRD4 phosphorylation in the nucleus accumbens (NAc) was closely related to the maintenance of cocaine reinforcement and relapse in different cocaine exposure paradigms. Cocaine significantly increased the binding of phosphorylated BRD4 (pBRD4) at the promoter of\n                    <jats:italic>Gria2<\/jats:italic>\n                    and\n                    <jats:italic>Bdnf<\/jats:italic>\n                    genes in the NAc. (+)JQ1, a selective BRD4 inhibitor, markedly reduced the reinforcement and reinstatement of cocaine\u2010seeking behaviors, which was accompanied by the decreased expressions of GRIA2 and BDNF. Furthermore, chromatin immunoprecipitation assay showed that (+)JQ1 clearly attenuated cocaine\u2010enhanced binding of pBRD4 at the promotor of\n                    <jats:italic>Gria2<\/jats:italic>\n                    and\n                    <jats:italic>Bdnf<\/jats:italic>\n                    genes. Blockade of casein kinase II significantly attenuated BRD4 phosphorylation and cocaine relapse\u2010like behaviors, suggesting the important role of pBRD4 in modulating cocaine effect. Together, our findings suggest that BRD4 phosphorylation in the NAc modulates multiple addiction\u2010related behaviors of cocaine and particularly relapse to cocaine\u2010seeking behaviors. Inhibition of BRD4 activity may be a novel target against cocaine addiction and relapse.\n                  <\/jats:p>","DOI":"10.1111\/adb.12808","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T01:24:30Z","timestamp":1564536270000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Role of\n                    <scp>BRD4<\/scp>\n                    phosphorylation in the nucleus accumbens in relapse to cocaine\u2010seeking behavior in mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Wei","family":"Guo","sequence":"first","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University  Yantai China"},{"name":"National Chengdu Center for Safety Evaluation of 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