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Accordingly, the DNA demethylation, induced by ten\u2010eleven translocation (Tet) enzymes, may represent a novel approach to prevent opioid addiction. The present study examined the role of TET1 and TET3 in the development of morphine\u2010seeking behavior in rats. We showed that 1 day of morphine self\u2010administration (SA) training upregulated TET3 but not TET1 expression in the hippocampal CA1. With 7 days of morphine SA training, the expression of TET3 in the CA1 returned to the baseline level, while the TET1 expression was downregulated. No change of TET1 and TET3 in the nucleus accumbens shell was observed in morphine SA trained rats, or in the yoked morphine rats, or in rats trained for saccharin SA. Furthermore, we found that knocking down TET3 expression in the CA1 accelerated the acquisition of morphine SA, while overexpression of the catalytic domain of TET1 in the CA1 attenuated the acquisition. Together, these findings suggest that TET1 and TET3 in the CA1 are important epigenetic modulators involved in the morphine\u2010seeking behavior and provide a new strategy in the treatment of opioid addiction.<\/jats:p>","DOI":"10.1111\/adb.12875","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T14:19:55Z","timestamp":1581085195000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Double dissociation of inhibitory effects between the hippocampal TET1 and TET3 in the acquisition of morphine self\u2010administration in rats"],"prefix":"10.1111","volume":"26","author":[{"given":"Feng\u2010Ze","family":"Jiang","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Mental Health, Institute of Psychology  Beijing China"},{"name":"Department of Psychology University of Chinese Academy of Sciences  Beijing 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