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However, the mechanisms regulating expression of <jats:italic>Bdnf<\/jats:italic> in drug addiction remain elusive. In the present study, using the conditioned place preference (CPP) model, we showed that expression of <jats:italic>Bdnf IV<\/jats:italic> is upregulated in the nucleus accumbens (NAc) of conditioned animals while <jats:italic>Bdnf I<\/jats:italic> is upregulated in cocaine-treated mice irrespective of conditioning. The methylation level of a putative c-MYB binding site in the promoter region of <jats:italic>Bdnf IV<\/jats:italic> was significantly decreased in the NAc under cocaine CPP conditioning but remained unchanged without conditioning, concurrently with increased binding of c-MYB to this site. Exon IV promoter\/luciferase reporter assays revealed that transactivation of <jats:italic>Bdnf<\/jats:italic> by c-MYB was blocked by methylation of this c-MYB binding site. Administration of methionine, a precursor of SAM, inhibited cocaine CPP, reversed demethylation of c-MYB binding site and induction of <jats:italic>Bdnf IV<\/jats:italic> expression by cocaine CPP. Our results imply that <jats:italic>Bdnf IV<\/jats:italic> demethylation at c-MYB binding site is involved in cocaine-triggered seeking behavior, whereas <jats:italic>Bdnf I<\/jats:italic> responds to the immediate pharmacological effects of cocaine.<\/jats:p>","DOI":"10.1038\/srep22087","type":"journal-article","created":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T10:56:20Z","timestamp":1456397780000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference"],"prefix":"10.1038","volume":"6","author":[{"given":"Weiping","family":"Tian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiesi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huajing","family":"Teng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moshe","family":"Szyf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong Sheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,2,25]]},"reference":[{"key":"BFsrep22087_CR1","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1073\/pnas.0711863105","volume":"105","author":"P Bekinschtein","year":"2008","unstructured":"Bekinschtein, P. et al. 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