褪黑素抑制可卡因诱导的条件性位置偏爱大鼠DNMT1的下调

Melatonin inhibites the down-regulation of DNMT1 expression in the conditioned place preference rats induced by cocaine

目的研究褪黑素拮抗大鼠可卡因诱导的条件性位置偏爱的作用和可能机制。方法建立可卡因诱导的条件性位置偏爱模型,诱导前30min给予褪黑素腹腔注射,检测实验大鼠条件性位置偏爱的变化,并应用Western blot、免疫荧光共聚焦激光扫描显微镜及real-time PCR技术,检测褪黑素对大鼠前额叶皮层中可卡因诱导的DMNT1表达的影响。结果褪黑素对可卡因诱导的大鼠条件性位置偏爱效应具有显著的抑制作用。共聚焦显微镜和Western blot结果表明,可卡因诱导大鼠前额叶皮层中DNMT1表达的减少,而褪黑素能够抑制可卡因的这种作用。Real-time PCR检测结果证明,可卡因诱导大鼠前额叶皮层中DNMT1 mRNA的下调,而褪黑素能够抑制这种作用。结论褪黑素可能通过抑制大鼠前额叶皮层中DNMT1表达的下调拮抗可卡因诱导的条件性位置偏爱。

Objective To investigate the effect and possible mechanism of melatonin（Mel） on the conditioned place preference（CPP） rat induced by cocaine. Methods The CPP model was established by injection of cocaine peritoneally, 30 min before that Mel was injected peritoneally. Then the change of CPP rats was detected, and the expression of DNA methyhransferase 1 （DNMT1） was determined by Western blot, confocal microscopy and real-time PCR. Results Mel significantly inhibited the CPP induced by cocaine. The results of confocal microscopy and Western blot showed that cocaine induced the decrease of DNMT1 protein expression in prefront cortex, but Mel inhibited the decrease of DNMT1 protein expression. The real-time PCR showed that cocaine induced the decrease of DNMT1 mRNA expression in prefront cortex, while Mel inhibited the decrease of DNMT1 mRNA expression. Conclusion The antagonit effect of Mel on CPP might be related to inhibiting the down-regulation of DNMT1.