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

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

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。

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）,metbamphetamine 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.