谷氨酸受体1与钩藤碱抑制甲基苯丙胺依赖斑马鱼条件性位置偏爱的关系  

Rhynchophylline reverses methamphetamine-induced CPP by regulating GluR1 expression in zebrafish

作　　者：朱晨 刘伟 李璟 陈志杰 李婵 周玉婷 莫志贤 ZHU Chen;LIU Wei;LI Jing;CHEN Zhi-jie;LI Chan;ZHOU Yu-ting;MO Zhi-xian(Dept of Traditional Chinese Medicine Pharmacology,School of Traditional Chinese Medicine,Southern Medical University,Guangzhou510515,China;Central Lab,Southern Medical University,Guangzhou510515,China)

机构地区：[1]南方医科大学中医药学院中药药理学教研室,广东广州510515 [2]南方医科大学中心实验室,广东广州510515

出　　处：《中国药理学通报》2019年第5期620-623,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81673628;81873030);广州市科技计划项目(No 201707010287)

摘　　要：目的研究钩藤碱对甲基苯丙胺(METH)依赖斑马鱼产生条件性位置偏爱(CPP)的影响,以及谷氨酸受体1(GluR1)对METH依赖斑马鱼的作用机制。方法斑马鱼随机分为5组:对照组、模型组、钩藤碱低剂量组(50 mg·kg^(-1))、钩藤碱高剂量组(100 mg·kg^(-1))和氯胺酮组(150 mg·kg^(-1))。斑马鱼腹腔注射METH后,进行CPP训练,建立斑马鱼METH依赖CPP模型,分析各组斑马鱼在CPP箱中的活动,采用免疫组化和Western blot等方法研究各组斑马鱼脑内GluR1的表达情况。结果腹腔注射METH 40 mg·kg^(-1)后,METH依赖斑马鱼CPP模型成功建立。与对照组相比,模型组斑马鱼在白箱中的停留时间明显增加;与模型组相比,钩藤碱高剂量组斑马鱼在白箱中的停留时间明显减少。与对照组相比,模型组斑马鱼脑内GluR1阳性细胞数及GluR1蛋白的表达明显增加;钩藤碱干预后,斑马鱼脑内GluR1阳性细胞数明显减少。结论钩藤碱在一定程度上可以抑制METH诱导斑马鱼产生CPP效应,其作用机制可能与斑马鱼脑内GluR1的表达有关。Aim To investigate the effect of rhynchophylline on methamphetamine (METH)-induced condition place preference (CPP) zebrafish and the relationship with GluR1. Methods METH was injected intraperitoneally to zebrafish,and the expression of GluR1 in zebrafish brain was detected by immunohistochemistry and Western blot. Results METH-induced CPP model was established after the administration of METH (40 mg·kg-1 ) in zebrafish.Compared to control group,the resident time in white box of model group zebrafish significantly increased;compared to model group,the resident time in white box of ketamine (150 mg·kg-1 ) group and rhynchophylline (100 mg·kg-1 ) group dramatically decreased.Compared to control group,the number of GluR1 positive cells and the GluR1 expression of model group zebrafish markedly increased;compared to model group,the number of GluR1 positive cells and the GluR1 expression of rhynchophylline group zebrafish evidently decreased. Conclusions GluR1 is important for METH-induced CPP formation in zebrafish.Further,rhynchophylline reduces GluR1 expression in METH-treated zebrafish brain,and its mechanism may be related to GluR1 expression in the brain of zebrafish.

关 键 词：钩藤碱 甲基苯丙胺 条件性位置偏爱 药物依赖 谷氨酸受体1 斑马鱼 

分 类 号：R-332[医药卫生] R284.1