Changes in the levels of DNA methyltransferases and demethylases in the nucleus accumbens in cocaine-induced behavioural sensitisation in rats with different exploratory activity
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Epigenetic modifications, such as DNA methylation, are involved in the development of cocaine-induced behavioural sensitisation. This study investigated the development and expression of cocaine-induced behavioural sensitisation in rats with high and low exploratory activity (HE and LE, respectively), and the drug-induced changes in the mRNA levels of Dnmt and Tet family genes in the nucleus accumbens. Only LE-animals had increased locomotor activity over continuous test sessions in response to repeated cocaine (12 mg/kg) administration and they developed a more pronounced behavioural sensitisation. Repeated cocaine treatment resulted in upregulated mRNA of Dnmt3b in HE-, but not in LE-rats, and upregulated mRNA levels of Tet3 in both. Thus, our results suggest that LE- and HE-rats differ in the development and expression of cocaine-induced behavioural sensitisation. The aim of future research is to further examine, whether the observed changes in Dnmt and Tet levels could explain the behavioural differences between HE- and LE-animals in response to cocaine.