Methylation in Syn and Psd95 genes underlie the inhibitory effect of oxytocin on oxycodone-induced conditioned place preference.

摘要: Abstract Oxycodone (Oxy) is one of the most effective analgesics in medicine, but associated with development dependence. Recent studies demonstrating epigenetic changes brain after exposure to opiates have provided an insight into possible mechanisms underlying addiction. Oxytocin (OT), endogenous neuropeptide well known for preventing drug abuse, a promising pharmacotherapy counteract Therefore, we explored mechanism Oxy addiction and role OT Oxy-induced alterations. In this study, drug-induced conditioned place preference (CPP), i.e. expression synaptic proteins density ventral tegmental area (VTA) were measured. We also sought identify DNA methyltransferases (DNMTs), ten-eleven translocations (TETs), global 5-methylcytosine (5-mC), methylation two genes implicated plasticity (Synaptophysin, Syn; Post-synaptic protein 95, Psd95). (3.0 mg/kg, i.p.) induced CPP acquisition Sprague-Dawley rats. down-regulated DNMT1 up-regulated TET1-3, leading decrease 5-mC levels differential demethylation at exon 1 Syn 2 Psd95. These Psd95 elevated (SYN, PSD95) VTA. Pretreatment (2.5 µg, i.c.v.) via its receptor specifically blocked CPP, normalized density, regulated TET2-3 causing reverse important gene regulation – could inhibit