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In this study, we evaluated the enzyme activity of DNA methyltransferases (DNMTs) after cocaine treatment and during withdrawal. Furthermore, we studied how genetic or pharmacological inhibition of DNMTs in mouse nucleus accumbens (NAc) affects the induction and expression of cocaine\u2010induced behavioral sensitization. Our results showed that after silencing <jats:italic>Dnmt3a<\/jats:italic> in the NAc during the induction phase of cocaine\u2010induced sensitization, overall DNMT activity decreases, correlating negatively with behavioral sensitization. Reduced <jats:italic>Dnmt3a<\/jats:italic> mRNA during this phase was the largest contributing factor for decreased DNMT activity. Cocaine withdrawal and a challenge dose increased DNMT activity in the NAc, which was associated with the expression of behavioral sensitization. Long\u2010term selective <jats:italic>Dnmt3a<\/jats:italic> transcription silencing in the NAc did not alter DNMT activity or the expression of cocaine\u2010induced behavioral sensitization. However, bilateral intra\u2010NAc injection of a non\u2010specific inhibitor of DNMT (RG108) during withdrawal from cocaine decreased DNMT activity in the NAc and had a small effect on the expression of cocaine\u2010induced behavioral sensitization. Thus, cocaine treatment and withdrawal is associated with biphasic changes in DNMT activity in the NAc, and the expression of behavioral sensitization decreases with non\u2010selective inhibition of DNMT but not with selective silencing of <jats:italic>Dnmt3a<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/adb.12720","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T20:48:30Z","timestamp":1549572510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The role of DNA methyltransferase activity in cocaine treatment and withdrawal in the nucleus accumbens of mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Mari","family":"Urb","sequence":"first","affiliation":[{"name":"Department of Pharmacology Institute of Biomedicine and Translational Medicine, University of Tartu  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