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To date, the roles of BRD4 and other BET proteins in substance use disorder (SUD) models have been mainly studied using small molecule inhibitors that block the bromodomain interactions with acetylated histones. In other disease models, non\u2010bromodomain BRD4\u2010protein interactions have also been shown to play an important role in BRD4's molecular functions, but these interactions have yet to be studied in SUD models. Here, using BRD4 co\u2010immunoprecipitation coupled to tandem mass spectrometry, we identified several putative BRD4\u2010interacting proteins in the nucleus accumbens (NAc) that are altered by acute or repeated cocaine exposure in male and female Sprague Dawley rats. In BRD4\u2010immunoprecipitated samples, gene ontology molecular function analysis revealed an enrichment of pathways associated with polymerase activity, SH3 domain binding, and chromatin\u2010protein\u2010adaptor activity in the cocaine treated groups. Notably, casein kinase 1 epsilon (CK1\u03b5), a protein previously implicated in SUDs, was identified as a putative BRD4\u2010interacting protein, and this association was increased following repeated cocaine injections. However, no significant change in total CK1\u03b5 protein expression was observed in the NAc via western blot following acute or repeated cocaine treatment. In additional experiments, we sought to determine the effects of CK1\u03b5 inhibition on the expression of a cocaine\u2010related memory. Pharmacological inhibition of CK1\u03b5 with PF\u20104800567 diminished the expression of cocaine conditioned place preference. In a separate cohort of rats, an acute injection of PF\u20104800567 did not alter locomotor activity and anxiety\u2010like behavior in the open field test. Collectively, these findings suggest that several novel proteins, including CK1\u03b5, may play a role in BRD4\u2010mediated molecular adaptations to cocaine exposure, and that CK1\u03b5 represents a potential target for future investigation in animal models of cocaine\u2010seeking behavior.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70336-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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