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  

EFFECT OF DOPAMINE D_3 RECEPTOR ON METHAMPHETAMINE INDUCED CONDITIONED PLACE PREFERENCE IN MICE

作　　者：孔晗[1] 刘彦玲[1] 朱杰[1] 阎春霞[1] 魏曙光[1] 张洪波[1] 李生斌[1] 陈腾[1] 

机构地区：[1]西安交通大学医学院法医系,西安710061

出　　处：《中国药物依赖性杂志》2009年第3期175-179,227,共6页Chinese Journal of Drug Dependence

基　　金：教育部"新世纪人才支持计划"项目(NCET-07-0662);国家自然科学基金(30572089)资助

摘　　要：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。Objectve： 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 independentsamples 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 10mg·kg^-1induced 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.

关 键 词：多巴胺D3受体 甲基苯丙胺 条件性位置偏爱 基因敲除 

分 类 号：R749.3[医药卫生—神经病学与精神病学] R595.5[医药卫生—临床医学]