Donnan G A, Kaczmarczyk S J, Solopotias T, Rowe P, Kalnins R M, Vajda F J, Mendelsohn F A
Clin Exp Neurol. 1986;22:155-64.
The recent discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a syndrome of Parkinsonism in man and monkey has stimulated the search for a small animal model of Parkinsonism. In this study, MPTP was administered to a series of small animals and observations made on clinical and neurochemical changes. The clinical effects of MPTP in rabbits, guinea pigs, and rats were short lived, and no chronic Parkinsonian syndrome developed. The C57 black mouse, however, although also not showing clinical changes, proved to be an ideal neurochemical model in which to study the effects of MPTP since striatal dopamine levels were reliably reduced to 13% of control values after 4 intraperitoneal injections of 30 mg/kg MPTP. Pathological study of the striatum and substantia nigra in the mouse model failed to show any alteration in neuronal morphology or numbers. Although the effect of MPTP on striatal dopamine lasted for up to 2 weeks after the last MPTP injection, the possibility exists that no neurotoxic effects occur and the observed dopamine depletion is pharmacological only.
最近发现1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）可在人和猴身上引发帕金森综合征，这刺激了对帕金森病小动物模型的研究。在本研究中，对一系列小动物给予MPTP，并对临床和神经化学变化进行观察。MPTP对兔、豚鼠和大鼠的临床作用持续时间较短，未出现慢性帕金森综合征。然而，C57黑小鼠虽然也未表现出临床变化，但被证明是研究MPTP作用的理想神经化学模型，因为在腹腔注射4次30mg/kg MPTP后，纹状体多巴胺水平可靠地降至对照值的13%。对小鼠模型的纹状体和黑质进行病理研究，未发现神经元形态或数量有任何改变。尽管在最后一次注射MPTP后，MPTP对纹状体多巴胺的作用可持续长达2周，但仍有可能不存在神经毒性作用，所观察到的多巴胺耗竭仅是药理学上的。
