重复注射鱼藤酮对中枢多巴胺神经元的毒性作用

目的 研究小剂量鱼藤酮长期暴露对大鼠和小鼠中枢多巴胺能神经元的损伤特点。方法 昆明小鼠和Wistar大鼠每日腹腔注射鱼藤酮(Rotenone)，连续40d。用小鼠攀爬笼检测阿扑吗啡(AFO)诱导的定型行为，以HPLC法检测血浆和脑组织鱼藤酮浓度以及脑皮层和纹状体多巴胺(DA)、二羟基苯乙酸(DOPAC)含量。结果 注射鱼藤酮20d，大鼠脑皮层和纹状体鱼藤酮明显蓄积，APO诱导的小鼠攀爬行为显著下降，纹状体DA和DOPAC含量也显著降低。鱼藤酮暴露20d和40d，纹状体DA和DOPAC含量均显著下降，且有明显的量效和时效关系。结论 重复注射鱼藤酮显著降低动物中枢多巴胺神经递质的含量并导致DA神经行为的异常。

Toxic effect of long-term exposure to rotenone on central dopaminergic nerve of rats and mice

Objective To observe the characteristics of damage induced by long term exposure to rotenone at low dose to the central dopaminergic nerve in rats and mice. Methods Kunming mice and Wistar rats were daily administrated with rotenone (ip) for 20 or 40 d. Apomorphine(APO) induced stereotyped behavior in mice was tested with a cylindrical wired mash. High performance liquid chromatography was used to determine the concentrations of rotenone in the blood plasma and brain tissues, dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the cortex and striatum, respectively. Results After 20 day consecutive exposure, rotenone was accumulated in the brain tissues and the climbing behavior of mice was depressed significantly. A further decrease in DA and DOPAC contents in the cortex and striatum was identified in the rats administrated with rotenone for 40 d. Conclusion Long term exposure to rotenone produces a remarkable decline of DA transmission and APO induced climbing behavior.