褪黑素通过抑制△FosB的表达拮抗大鼠可卡因条件性位置偏爱的复燃

Melatonin antagonizes reinstatement of the conditioned place preference induced by cocaine through inhibiting the expression of △FosB

目的研究褪黑素对大鼠可卡因条件性位置偏爱复燃的作用及机制。方法建立大鼠可卡因诱导的条件性位置偏爱模型,在可卡因戒断后/复燃前给予褪黑素,检测实验大鼠条件性位置偏爱的变化,并应用Western blot和共聚焦激光扫描显微镜技术观察褪黑素对△FosB表达的影响;另外进行松果体摘除术,观察去除内源性褪黑素对可卡因诱导的条件性位置偏爱和△FosB表达的影响。结果褪黑素对大鼠条件性位置偏爱效应的复燃具有抑制作用,褪黑素下调了可卡因复燃诱导的△FosB在相关脑区的高表达。松果体摘除抑制了可卡因诱导的条件性位置偏爱的形成,但是对复燃诱导的条件性位置偏爱的强化无明显作用,松果体摘除组大鼠除了在海马表现出△FosB的低表达外,在其它脑区未观察到明显变化。结论褪黑素可能通过抑制可卡因复燃诱导的△FosB的高表达拮抗大鼠可卡因奖赏效应的强化。

Objective To investigate the effect and mechanism of melatonin（Mel） on reinstatement of the conditioned place preference（CPP） induced by cocaine. Methods Firstly, a cocaine induced CPP model was established, Mel was given after cocaine withdrawal, i.e. before reinstatement, and then the change of CPP rats was detected. The expression of △FosB was observed by western blotting and confocal microscopy. Results Mel inhibited the reinstatement of CPP induced by cocaine priming and downregulated high expression of the △ FosB during cocaine relapse in relevant brain regions. Pinealectomy inhibited the formation of the CPP induced by cocaine but was of no significant effect on the CPP induced by cocaine priming. The expression level of △ FosB was lower in hippocampus but not in other relevant brain regions in pinealectomy group than in CPP model group. Conclusion That Mel antagonised reinforcement of cocaine reward might be related to inhibiting the higher expression of △FosB induced by cocaine relapse.