Schneider J S, Kovelowski C J
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102.
Brain Res. 1990 Jun 11;519(1-2):122-8. doi: 10.1016/0006-8993(90)90069-n.
Cognitive deficits which may occur following chronic low-dose exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in monkeys who remained motor asymptomatic for parkinsonism throughout the study. The tasks used to assess cognitive functioning are those which have proved in the past to be sensitive to disruption of frontal cortical and or striatal integrity (delayed response and delayed alternation) or sensitive to inferior temporal lobe dysfunction (visual pattern discrimination). Since Parkinson's disease patients have been described as exhibiting frontal signs, we were interested to examine whether MPTP-treated monkeys might exhibit deficits on frontally-mediated tasks, without the confound of motor disturbances. We found that macaque nemistrina monkeys exposed to cumulative doses of 14.94-75.42 mg of MPTP over periods ranging from 5 to 13 months never developed parkinsonian motor signs. However, all 4 animals examined showed significant post-MPTP deficits in delayed response and delayed alternation performance, while visual pattern discrimination performance remained intact. These animals also developed other behavioral problems including irritability and decreased attentiveness. These results show that MPTP can cause specific cognitive deficits independent of the motor deficits which can be produced by this toxin.
在整个研究过程中对帕金森病运动无症状的猴子进行了研究，以探究长期低剂量接触1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）后可能出现的认知缺陷。用于评估认知功能的任务是那些过去已被证明对额叶皮质和/或纹状体完整性破坏敏感（延迟反应和延迟交替）或对颞下回功能障碍敏感（视觉模式辨别）的任务。由于帕金森病患者被描述为表现出额叶体征，我们有兴趣研究经MPTP处理的猴子是否可能在额叶介导的任务上表现出缺陷，而不存在运动障碍的混淆因素。我们发现，在5至13个月的时间里累计接触14.94 - 75.42毫克MPTP的猕猴从未出现帕金森病运动体征。然而，所检查的所有4只动物在MPTP处理后延迟反应和延迟交替表现方面均出现显著缺陷，而视觉模式辨别表现保持完整。这些动物还出现了其他行为问题，包括易怒和注意力下降。这些结果表明，MPTP可导致特定的认知缺陷，独立于该毒素可能产生的运动缺陷。
