Guttman M, Fibiger H C, Jakubovic A, Calne D B
Belzgerg Laboratory of Clinical Neuroscience, University of British Columbia, Vancouver, Canada.
J Neurochem. 1990 Apr;54(4):1329-34. doi: 10.1111/j.1471-4159.1990.tb01966.x.
Cynomolgus monkeys received intracarotid injections of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce a chronic unilateral model of parkinsonism. Extensive dopamine (DA) depletion was observed in the caudate nucleus and putamen on the side ipsilateral to the injection and this was associated with contralateral tremor, rigidity, and bradykinesia. A dose of 1.25 mg of MPTP caused ipsilateral DA loss of 99.4% in the caudate nucleus, 99.8% in the putamen, and 74.2% in the nucleus accumbens. A dose of 2.5 mg caused ipsilateral DA depletion of 99.3% in the caudate nucleus, 99.5% in putamen, and 90.1% in the nucleus accumbens. The unilateral aspect of the lesion was dose sensitive, with the 2.5-mg dose causing bilateral asymmetric DA depletion. Tissue concentrations of serotonin were not affected by the toxin. These findings confirm that intracarotid injection of MPTP may produce a useful primate model of hemiparkinsonism that can be associated with selective unilateral DA depletion when the appropriate dose of toxin is used.
食蟹猴接受了颈内注射神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），以建立帕金森病的慢性单侧模型。在注射侧同侧的尾状核和壳核中观察到广泛的多巴胺（DA）耗竭，这与对侧震颤、僵硬和运动迟缓有关。1.25毫克的MPTP剂量导致尾状核同侧DA损失99.4%，壳核中为99.8%，伏隔核中为74.2%。2.5毫克的剂量导致尾状核同侧DA耗竭99.3%，壳核中为99.5%，伏隔核中为90.1%。损伤的单侧性对剂量敏感，2.5毫克剂量导致双侧不对称DA耗竭。血清素的组织浓度不受毒素影响。这些发现证实，当使用适当剂量的毒素时，颈内注射MPTP可能产生一种有用的半侧帕金森病灵长类模型，该模型可与选择性单侧DA耗竭相关。
