MPTP对小鼠行为学及脑纹状体多巴胺含量的影响

目的观察不同剂量对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）小鼠行为学及脑纹状体多巴胺（DA）去甲肾上腺素（NE）、5-羟色胺（5-HT）及其代谢产物含量的影响，探讨MPTP致帕金森病（PD）样小鼠模型的最佳条件。方法 C57BL小鼠分别给予MPTP不同单日剂量（20～40mg/ kg），不同给药次数（1～7）天处理，测定各组小鼠爬杆时间检测动物运动协调性，测定自发活动记数评价动物神经兴奋性，测定通道式水迷宫游出时间评价各组小鼠空间学习记忆能力。应用高效液相色谱法检测动物纹状体内DA、NE、5-HT及其代谢产物含量。结果 MPTP30mg/kg腹腔注射1天、3天、7天及40mg/ kg腹腔注射1天、3天后小鼠都出现不同程度爬杆时间延长，自发活动次数减少，但小鼠水迷宫游出时间在给药前后未见明显改变。MPTP处理组与对照组相比DA及其代谢产物3，4-二羟基苯乙酸（DOPAC）含量都有明显降低，而NE、5-HT、及其代谢产物5-羟吲哚乙酸（5-HIAA）含量均未见明显改变。结论 MPTP处理可造成小鼠的帕金森病样症状，但不伴有明显智力障碍。在此种动物模型中，应根据科研目的选择MPTP的应用剂量和给药途径。

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on behavior and dopamine content of stratium in mice

Objective　 To observe the behavior and content of dopamine（DA）,norepinephrine(NA),5-hydroxytryptamine(5-HT) in stratium of mice treated with different doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). Methods　C57BL mice were treated with different doses of MPTP, then the pole test was conducted to determine the motor harmony , spontaneous motor activity was determined to test the excitability and modified watermaze was used to determine the learning- memory ability of mice. The content of DA, 5-HT,NA and their metabolites in stratium of different groups of mice was determined with high performance liquid chromatograph (HPLC).Results　All the mice intraperitoneal injected with MPTP at the dose of 30mg/　kg lasted 1 to 7 days and at the dose of 40mg/　kg lasted 1 to 3 days showed different disability in pole test and decrease of spontaneous motor activity,but there was no difference among different groups in watermaze test. All MPTP treated mice showed dominant decrease in content of DA and 3,4-dihydroxyphenylacetic acid (DOPAC). But there was no difference in content of NA,5-HTand their metabolites between different groups. Conclusion　Mice treated with MPTP can manifest parkinsonism without dominant decrease in learning-memory ability. In this model , we should use different dose of MPTP and different drug administration path to obtain our prospective goals.