RGS4和D2受体信号通路相关分子在甲基苯丙胺依赖CPP大鼠纹状体的表达变化

目的:研究甲基苯丙胺(methamphetamine, METH)依赖条件性位置偏爱(conditioned place preference, CPP) 实验大鼠纹状体G蛋白信号调节因子4(regulator of G-protein signal 4,RGS4)和多巴胺D2受体(dopamine receptor D2)信号通路相关分子的表达变化。方法: 建立METH依赖CPP大鼠 1周组、2周组，应用蛋白质印迹(Western blot)测定各组大鼠纹状体RGS4和D2、抑制性G蛋白α亚基(inhibitory G protein α-subunit,Gαi)、丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)蛋白表达的变化；应用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)测定各组大鼠纹状体环磷酸腺苷(cyclic adenosine monophosphate,cAMP)含量的变化。结果: 与生理盐水对照组相比，METH依赖1周组、2周组大鼠在伴药箱的平均停留时间明显延长(P<0.05)。与生理盐水对照组相比，RGS4蛋白在METH依赖1周、2周组的表达均明显下降(P<0.01)，且与METH依赖1周组相比，2周组的下降更为明显(P<0.05)；与生理盐水对照组相比， D2、Gαi、MAPK蛋白以及cAMP在METH依赖1周、2周组的表达均明显升高(P<0.01)，且与METH依赖1周组相比，2周组的升高更为明显(P<0.05)。结论:在METH依赖的CPP大鼠纹状体中，RGS4和D2受体信号传导通路相关分子发生了改变，RGS4可能参与了METH依赖的CPP大鼠纹状体D2受体信号传导通路的调节。

Expression of RGS4 and D2 receptor signaling pathway in striatum of methamphetamine-dependent CPP rats

AIM: To study the expression of signal transduction molecules in the striatum G protein protein 4 (RGS4) and dopamine D2 receptor (D2) in conditioned place preference (CPP) rats treated with methamphetamine (meth). METHODS: METH dependence CPP model was established (1 week and 2 weeks of METH dependence groups), The protein expression of RGS4 and D2, inhibitory G protein alpha-subunit (Gαi), mitogen-activated protein kinase (MAPK) in striatum were determined by Western blotting (WB). The changes of cyclic adenosine monophosphate (cAMP) content in striatum of rats were determined by enzyme linked immunosorbent assay (ELISA).RESULTS:Compared with saline control group, the average time of rats in the methamphetamine-paired chamber for two groups was increased (P<0.05). Compared with saline control group, RGS4 protein expressions in the two METH dependent groups were reduced (P<0.01); compared with 1 week of METH dependence group, that of 2 weeks group was reduced significantly (P<0.05). D2, Gαi, MAPK protein and cAMP expressions in the two METH dependent groups were increased (P<0.01); compared with 1 week of METH dependence group, those of 2 weeks were increased significantly (P<0.05). CONCLUSION: RGS4 and D2 receptor signaling pathways in striatum have changed in METH dependent rats, RGS4 may be involved in the regulation of METH-dependent D2 receptor signaling pathway in METH dependent rats.