【摘要】 目的:探讨多巴胺受体对可卡因诱导的MAPK通路及c-fos基因表达的调控作用。方法:应用多巴胺受体基因敲除小鼠模型,采用Western blotting检测可卡因作用后2h,MAPK家族成员ERK,JNK和p38蛋白激酶的磷酸化活化,及早期反应基因c-fos的基因表达。结果:可卡因急性作用下,D1多巴胺受体促进CPu区ERK激酶的激活和c-fos基因的诱导表达,D3多巴胺受体抑制CPu区ERK激酶的激活和c-fos基因的诱导表达。而p38和JNK没有被可卡因激活。ERK激酶的特异性抑制剂SL327可以阻断可卡因对c-fos基因的激活。结论:D1和D3多巴胺受体对ERK激酶的激活和c-fos基因的诱导表达起相反的调节作用,并且c-fos基因的诱导表达依赖于ERK信号通路。更多还原

【Abstract】 AIM: To investigate the role of D1 and D3 dopamine receptor on MAPK signal transduction and c-fos gene expression after acute cocaine treatment. METHODS: Activations of extracellular signal-regulated kinase (ERK), the c-Jun N-terminal kinase (JNK), p38 activation and expression of c-fos in wild type and D1 and D3 receptor mutant mice after acute cocaine treatment were checked by Western blotting. RESULTS: ERK activation and c-fos induction was enhanced in D3 mutant mice and abolished in D1 mutant mice by acute cocaine treatment, while p38 and JNK activation was not obviously modulated by the D1 and D3 receptors by acute cocaine treatment. Meanwhile, c-fos induction was inhibited when SL327, a specific MEK inhibitor, was injected before cocaine treatment. CONCLUSION: D1 and D3 receptors play opposite roles in the regulation of ERK activation and c-fos gene expression after acute cocaine treatment. The expression of c-fos gene depends on ERK signal pathway after acute cocaine treatment.更多还原