甲基苯丙胺依赖大鼠纹状体RGS4和D2受体信号传导通路mRNA的表达

The Changes of mRNA of RGS4 and D2 Receptor Signal Transduction in Striatum of Methamphetamine Dependent Rats

目的通过建立甲基苯丙胺(methamphetamine,MA)依赖大鼠模型,检测其纹状体G蛋白信号调节因子4(regulator of G-protein signaling 4,RGS4)、多巴胺D2受体(dopamine receptor D2,DRD2)、抑制性G蛋白α亚基(inhibitory G proteinα-subunit,Gαi)和丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)的m RNA表达变化,探讨MA依赖对RGS4、D2信号通路的影响.方法通过腹腔注射MA,建立MA条件性位置偏爱(conditioned place preference,CPP)1周组、2周组模型,应用实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-PCR)测定各组大鼠纹状体RGS4 m RNA、DRD2 m RNA、Gαi m RNA和MAPK m RNA的表达变化.结果与生理盐水对照组比较大鼠在伴药箱的平均停留时间MA依赖CPP-周组、2周组均延长,差异具有统计学意义(P<0.05),提示MA依赖大鼠CPP模型成功建立.与生理盐水对照组比较,RGS4m RNA在MA依赖CPP 1周组、2周组中表达均降低,且2周组下降趋势更明显,但差异无统计学意义(P>0.05);而与生理盐水对照组比较MA依赖CPP 2周组中DRD2 m RNA、Gαi m RNA和MAPK m RNA的表达均明显上调,差异有统计学意义(P<0.05).结论在MA依赖中,RGS4和D2受体信号通路发生变化,RGS4可能为D2信号通路的调节靶点.

Objective The model of methamphetamine （MA） dependent rats was established to detect the changes of mRNA expression of regulator of G-protein signal 4 （RGS4） , dopamine receptor D2 （DRD2） , inhibitory G protein α -subunit （G α i）, and the change of mitogen-activated protein kinase （MAPK） in striatum. To explore the effect of MA dependence on RGS4 and D2 receptor signal transduction. Methods The MA dependent rats model of conditioned place preference （CPP） 1 week group （group 1） and 2 weeks group （group 2） was established by administered with MA （ip） using CPP method. The mRNA expressions of RGS4, DRD2, Gα iand MAPK in striatum were determined by real-time quantitative polymerase chain reaction （RT-PCR） Results Compared with saline control group, the average detention time of rats in the methamphetamine-paired chamber for two groups were increased （P〈0.05） , which showed that model was established successfully. Compared with saline control group, RGS4mRNA expressions on the two MA dependent CPP groups were reduced, but there were no significant differences （P 〉0.05） Compared with saline control group, DRD2mRNA, G αimRNA and MAPKmRNA expressions on group 2 were increased obviously in striatum, and the differences were significantly （P〈0.05） Conclusion RGS4 and D2 receptor signal transduction have changed in MA dependent rats, and RGS4 may regulate the D2 receptor signal transduction by certain mechanism.