Filion M, Tremblay L, Bédard P J
Centre de Recherche en Neurobiologie, Université Laval et Hôpital de l'Enfant-Jésus, Québec, Canada.
Brain Res. 1991 Apr 26;547(1):152-61.
The mixed (D1 and D2) dopamine agonist apomorphine was injected (10-200 micrograms/kg, s.c.) to cynomolgus monkeys before and after they were rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Motor behavior was examined together with corresponding neuronal activity in the external (GPe) and internal (GPi) segments of the globus pallidus, including a small population of neurons localized within the GPe and displaying a characteristic discharge at low frequency with bursts (LFB), and border (Bor) neurons localized at the periphery of the pallidal segments. In the intact animal strong but not weak doses of the drug induced generalized agitation without apparent neuronal effects. In 1 parkinsonian animal that showed some recuperation of normal behavioral and pallidal activity, weak doses induced agitation and partly reduced the signs of parkinsonism, again without apparent neuronal effects. The same results were obtained before day 21 after MPTP in a parkinsonian monkey that did not recuperate. After day 21, however, the drug acted at a shorter latency, completely abolished the signs of parkinsonism, induced dyskinesia, increasing with repetition of injections, and clear neuronal effects. The same results were obtained from the start in another monkey in which recordings were begun 398 days after MPTP. Nearly all GPi neurons decreased their firing rate following apomorphine. The reverse was true of the predominant neuronal population in the GPe. In both cases, the intensity of the changes in firing rate varied much between neurons following the same dose of apomorphine. When the changes in firing rate were moderate or null, abnormal bursting firing patterns were normalized. Both LFB and Bor neurons decreased their firing rate following apomorphine; LFB neurons being extremely sensitive. The selective D2 agonist RU-24213 induced behavioral and neuronal effects identical to those of apomorphine.
在食蟹猴被1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导成帕金森病模型之前和之后，注射混合（D1和D2）多巴胺激动剂阿扑吗啡（10 - 200微克/千克，皮下注射）。观察运动行为，并同时检测苍白球外部（GPe）和内部（GPi）节段相应的神经元活动，包括一小部分位于GPe内且以低频爆发放电（LFB）为特征的神经元，以及位于苍白球节段周边的边界（Bor）神经元。在未患病动物中，强剂量而非弱剂量的药物会引发全身性躁动，但无明显的神经元效应。在1只表现出一定程度正常行为和苍白球活动恢复的帕金森病动物中，弱剂量药物引发躁动并部分减轻帕金森病症状，同样无明显的神经元效应。在MPTP处理后第21天之前，一只未恢复的帕金森病猴也得到了相同结果。然而，在第21天之后，药物起效潜伏期缩短，完全消除帕金森病症状，诱发运动障碍，且随着注射次数增加而加重，同时出现明显的神经元效应。在另一只MPTP处理398天后开始记录的猴中，从一开始就得到了相同结果。几乎所有的GPi神经元在注射阿扑吗啡后放电频率降低。GPe中的主要神经元群体则相反。在这两种情况下，相同剂量阿扑吗啡作用后，不同神经元放电频率变化的强度差异很大。当放电频率变化适中或无变化时，异常的爆发性放电模式恢复正常。LFB和Bor神经元在注射阿扑吗啡后放电频率均降低；LFB神经元极其敏感。选择性D2激动剂RU - 24213诱导的行为和神经元效应与阿扑吗啡相同。
