南方医科大学学报

南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (11): 1541-.

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钩藤碱对甲基苯丙胺依赖斑马鱼行为学的影响及机制

陈毅飞，彭菊，房淼，刘怡，聂玲辉，莫志贤，朱玲玲   

  • 出版日期:2016-11-20 发布日期:2016-11-20

Effect of rhynchophylline on behaviors of methamphetamine-dependent zebrafish and the mechanism

  • Online:2016-11-20 Published:2016-11-20

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摘要： 目的观察钩藤碱对甲基苯丙胺诱导斑马鱼条件性位置偏爱的影响，并探讨其相关机制。方法实验分空白对照组、甲基 苯丙胺模型组、模型+钩藤碱低剂量组（50 mg/kg）、模型+钩藤碱高剂量组（100 mg/kg）和模型+氯胺酮组（150 mg/kg）。条件性 位置偏爱训练方法建立甲基苯丙胺诱导的斑马鱼CPP模型。Noldus Ethovision XT system测试斑马鱼在非位置偏爱箱（伴药 箱）的停留时间以及在CPP箱的运动路线图。利用western blotting 的方法检测斑马鱼脑中NR2B、TH和GLUR2 三种蛋白表 达。结果与空白组相比，模型组斑马鱼训练前后在伴药箱停留的时间变化以及运动距离有显著性差异（P<0.05），NR2B、TH和 GLUR2三种蛋白表达的OD值也有显著性差异（P<0.05）。与模型组相比，高剂量钩藤碱组斑马鱼在伴药箱停留的时间变化以 及运动距离均具显著性差异（P<0.05），NR2B、TH和GLUR2三种蛋白表达的OD值也有显著性差异（P<0.05）。结论钩藤碱对 斑马鱼的甲基苯丙胺依赖有一定的抑制作用，其机制与干预脑内TH、NR2B、GLUR2蛋白表达有关。

Abstract: Objective To observe the effect of rhynchophylline on methamphetamine-dependent zebrafish and explore the possible mechanism. Methods Zebrafish were divided into control group, amphetamine group, low- (50 mg/kg) and high (100 mg/kg)-dose rhynchophylline groups, and ketamine (150 mg/kg) group. Conditioned place preference (CPP) was induced in zebrafish with methamphetamine, and the staying time in the drug box and the tracking map of the zebrafish were observed with Noldus Ethovision XT system. The protein expressions of TH, NR2B and GLUR2 in the brain of zebrafish with CPP were detected with Western blotting. Results Compared with the control group, zebrafish in methamphetamine group showed significant variations in the staying time and swimming distance in the drug box after conditioning (P<0.05) with obvious alterations of NR2B, TH and GLUR2 expressions in the brain (P<0.05). Treatment of methamphetamine-dependent zebrafish with high-dose rhynchophylline significantly reduced the variations in the staying time and swimming distance in the drug box (P<0.05) and in the expressions of NR2B, TH and GLUR2 in the brain (P<0.05). Conclusion Rhynchophylline can inhibit methamphetamine dependence in zebrafish, the mechanism of which may involve the expressions of TH, NR2B and GLUR2 proteins in the brain.