甲基苯丙胺诱导的小鼠条件性位置偏爱及多巴胺D_3受体的调制作用

目的:研究甲基苯丙胺(MA)对小鼠条件性位置偏爱(CPP)形成和复吸的影响,同时探讨多巴胺D3受体在此过程中的作用。方法:采用CPP系统,以多巴胺D3受体基因敲除(D3RKO)小鼠及具有相同遗传背景的野生型(WT)小鼠为对象,腹腔注射(ip)不同剂量(2mg·kg-1、5mg·kg-1、10mg·kg-1)甲基苯丙胺,观察给药前后小鼠CPP形成和复吸的行为改变,采用SPSS13.0统计软件包对实验数据进行单因素方差分析和独立样本t检验,以P<0.05为检验水准。结果:甲基苯丙胺2mg·kg-1不能使WT小鼠产生CPP效应,但能使D3RKO小鼠产生CPP效应,CPP消退后再次给药激发均无复吸效应;甲基苯丙胺5mg·kg-1能使WT和D3RKO小鼠均产生CPP效应,消退后再次给药激发,WT小鼠无复吸效应,而D3RKO小鼠出现复吸效应;甲基苯丙胺10mg·kg-1能使D3RKO小鼠产生CPP效应,无复吸效应,而WT小鼠未产生CPP效应。结论:甲基苯丙胺诱导下,D3RKO小鼠较野生型小鼠更容易形成CPP效应,也更容易发生复吸,提示多巴胺D3受体在甲基苯丙胺成瘾中发挥了一定作用,可能对甲基苯丙胺诱导的依赖和复吸具有抑制作用。

EFFECT OF DOPAMINE D3 RECEPTOR ON METHAMPHETAMINE INDUCED CONDITIONED PLACE PREFERENCE IN MICE

Objective:To investigate the conditioned place preference (CPP)induced by methamphetamine (MA)and the effect of dopamine D3 receptor on MA induced CPP. Methods:We observed the induction,extinction and reinstatement of CPP in dopamine D3 receptor knock-out (D3RKO)mice and C57BL/6J×129Sv wild-type mice with the same genetic background after administration of MA with different doses. Time spent in the drug-paired side was analyzed and One-Way AVONA test and independent-samples T test were adopted for statistical evaluation. Results:MA 2 mg·kg-1 induced CPP in D3RKO mice,then reinstated it,while this dose did not induce CPP in C57BL/6J×129Sv mice. MA 5 mg·kg-1 induced CPP in C57BL/6J×129Sv mice,then reinstated it. Also,MA 5 mg·kg-1 induced CPP in D3RKO mice,then reinstated it. MA 10 mg·kg-1 induced CPP in D3RKO mice,then could not reinstate it. Conclusion:Addiction is more easily induced by MA in D3RKO mice,compared with C57BL/6J×129Sv mice,which shows that dopamine D3 receptor suppresses the formation and reinstatement of CPP.