Ogawa N, Hirose Y, Ohara S, Ono T, Watanabe Y
Res Commun Chem Pathol Pharmacol. 1985 Dec;50(3):435-41.
A neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces pathological changes similar to human idiopathic Parkinson's disease in animals, was injected in mice for biochemical and pharmacological studies. The dopamine concentration showed a marked decrease (-75%) in the striatum 1-2 weeks after the injection of MPTP (30 mg/kg i.p. twice a day for 5 days; a total dose, 300 mg/kg) but no changes or only slight decreases in other brain regions. The norepinephrine concentration also decreased to half the preadministration level in the striatum. These changes closely resembled those observed in the brain of parkinsonian patients. An examination for evaluating bradykinesia of MPTP-treated mice (pole test) devised by the author revealed that bradykinesia was alleviated dose-dependently by injection of L-DOPA. These results suggested that MPTP-treated mice are a useful experimental model for the study of parkinsonism, and that the pole test using these animals is of value in the screening of anti-parkinsonian agents.
一种神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP),它在动物身上会产生与人类特发性帕金森病相似的病理变化,被注射到小鼠体内用于生化和药理学研究。在注射MPTP(30毫克/千克腹腔注射,每天两次,共5天;总剂量300毫克/千克)后1至2周,纹状体中的多巴胺浓度显著下降(-75%),但其他脑区没有变化或仅有轻微下降。去甲肾上腺素浓度在纹状体中也降至给药前水平的一半。这些变化与帕金森病患者大脑中观察到的变化非常相似。作者设计的用于评估MPTP处理小鼠运动迟缓的测试(杆试验)表明,注射左旋多巴可使运动迟缓呈剂量依赖性缓解。这些结果表明,MPTP处理的小鼠是研究帕金森病的有用实验模型,并且使用这些动物进行的杆试验在筛选抗帕金森病药物方面具有价值。