钩藤碱对甲基苯丙胺依赖小鼠位置偏爱和海马谷氨酸受体1表达的影响

目的:观察钩藤碱对甲基苯丙胺依赖小鼠位置偏爱和海马谷氨酸受体1(GluR1)蛋白表达的影响。方法:随机将50只小鼠分为5组:空白对照组,甲基苯丙胺模型组(4 mg·kg-1),氯胺酮(15 mg·kg-1)组,钩藤碱低剂量(40 mg·kg-1)组,钩藤碱高剂量(80 mg·kg-1)组,每组每天给予相应的药物,连续4 d,建立小鼠位置偏爱模型;免疫组化法和Western blot法检测GluR1蛋白的表达。结果:与正常对照组比较,模型组小鼠在伴药箱中逗留的时间明显增多(P<0.01),成功复制甲基苯丙胺依赖的小鼠位置偏爱模型,与模型组比较,氯胺酮组、钩藤碱低、高剂量组均可以明显减少小鼠在白箱逗留的时间(P<0.01)。免疫组化结果显示,甲基苯丙胺模型组与正常对照组相比蛋白GluR1表达明显增强(P<0.01),而与模型组比较,氯胺酮组、钩藤碱低剂量和高剂量组蛋白GluR1表达减少(P<0.01);Western blot结果显示,与正常对照组比较,模型组GluR1蛋白表达量明显上调(P<0.01),与模型组比较,氯胺酮组、钩藤碱低剂量和高剂量组GluR1蛋白表达下调(P<0.01)。结论:GluR1蛋白在甲基苯丙胺依赖小鼠位置偏爱形成中发挥着重要作用。

Effect of Rhynchophylline on Expression of Glutamate Receptor 1 in Methamphetamine-dependent Mice on Conditioned Place Preference

Objective: To study the effect of rhynchophylline(Rhy) on glutamate receptor 1 (GluR1) subunit in hippocampus of methamphetamine-induced conditioned place preference (CPP)mice. Method: Mice were randomly divided into five groups randomly with 10 mice in each group:normal control group, methamphetamine model group, methamphetamine with Rhy (40 mg·kg^-1), methamphetamine with Rhy (80 mg·kg^-1), methamphetamine with ketamine (15 mg·kg^-1). Each respective drug was administered daily for 4 days. Established place preference mice models were induced by methamphetamine,to observe the expression of GluR1 was observed by immunohistochemistry technique and Western blot. Result: Compared with normal control group, the time of mice with methamphetamine model group in non-preferred compartment increased significantly (P<0.01), indicating that methamphetamine place preference model was successfully established. Compared with methamphetamine model group, ketamine (15 mg·kg^-1),Rhy (40 mg·kg^-1)and Rhy (80 mg·kg^-1) reduced the time spent on white compartment of CPP mice significantly(P<0.01).Immunohistochemistry showed that the expression of GluR1 in hippocampus was increaseding in the methamphetamine model group(P<0.01), while in the ketamine group, low and high doseage Rhy were decreasing(P<0.01);Western blot showed that the express of GluR1 protein was significantly increased in the model group(P<0.01), while in the ketamine group, low and high doseage Rhy group were significantly decreasing(P<0.01). Conclusion: GluR1 protein plays an important role in the formation of methamphetamine-induced place preference in mice.