Willis G L, Savulescu J, Horne M K, Smith G C
Monash University, Department of Psychological Medicine, Prince Henry's Hospital, Melbourne, Victoria, Australia.
Brain Res Bull. 1987 Jul;19(1):57-61. doi: 10.1016/0361-9230(87)90165-1.
The selective neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected (IV) into monkeys (Macaca fascicularis) in two different injection regimes. With the small dose regime, one monkey was injected with 0.25 mg/kg, every other day, over a 16 day period. In the large dose regime, another monkey was injected with 0.5 mg/kg every other day, over an 8 day period. While the time required for drug delivery was varied between animals, the total dose delivered was 2 mg/kg in both animals. Before, during and for 14 days after the course of drug administration both animals were assessed on several motor function tests. The animal receiving the small dose regime showed normal motor performance on all tests for the duration of the study, however, the monkey receiving the large dose regime displayed progressive akinesia, muscular rigidity, and aphagia. In fact, impairment was so severe that this animal had to be force fed and maintained with daily oral L-dopa. Fluorescent histochemical assessment of forebrain in both monkeys revealed that striatal tissue was totally devoid of fluorescence in both cases. Large, swollen axons in the internal capsule, hypothalamus and midbrain were visible only in the severely impaired animal. These results suggest that, as with other neurotoxins, degeneration associated increases in amines may be important in the aetiology of Parkinson-like motor impairment produced by selective neurotoxins.
将选择性神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）通过静脉注射（IV）给予猕猴（食蟹猴），采用两种不同的注射方案。在小剂量方案中，一只猴子每隔一天注射0.25mg/kg，持续16天。在大剂量方案中，另一只猴子每隔一天注射0.5mg/kg，持续8天。虽然给药所需时间在不同动物之间有所不同，但两只动物的总给药剂量均为2mg/kg。在给药过程之前、期间以及给药后14天，对两只动物进行了多项运动功能测试评估。接受小剂量方案的动物在整个研究期间的所有测试中均表现出正常的运动能力，然而，接受大剂量方案的猴子出现了进行性运动不能、肌肉僵硬和吞咽困难。事实上，损伤非常严重，这只动物不得不通过强制喂食并每日口服左旋多巴来维持。对两只猴子前脑的荧光组织化学评估显示，在两种情况下纹状体组织均完全没有荧光。仅在严重受损的动物中可见内囊、下丘脑和中脑中有大的、肿胀的轴突。这些结果表明，与其他神经毒素一样，胺类物质相关的变性增加可能在选择性神经毒素引起的帕金森样运动损伤的病因学中起重要作用。
