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首页> 外文期刊>Neurobiology of disease >Nicotine-mediated improvement in l-dopa-induced dyskinesias in MPTP-lesioned monkeys is dependent on dopamine nerve terminal function
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Nicotine-mediated improvement in l-dopa-induced dyskinesias in MPTP-lesioned monkeys is dependent on dopamine nerve terminal function

机译：尼古丁介导的MPTP损伤的猴子的l-多巴诱发的运动障碍的改善取决于多巴胺神经末梢功能

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l-Dopa-induced dyskinesias (LIDs) are abnormal involuntary movements that develop with long term l-dopa therapy for Parkinson's disease. Studies show that nicotine administration reduced LIDs in several parkinsonian animal models. The present work was done to understand the factors that regulate the nicotine-mediated reduction in LIDs in MPTP-lesioned nonhuman primates. To approach this, we used two groups of monkeys, one with mild-moderate and the other with more severe parkinsonism rendered dyskinetic using l-dopa. In mild-moderately parkinsonian monkeys, nicotine pretreatment (300μg/ml via drinking water) prevented the development of LIDs by ~75%. This improvement was maintained when the nicotine dose was lowered to 50μg/ml but was lost with nicotine removal. Nicotine re-exposure again decreased LIDs. By contrast, nicotine treatment did not reduce LIDs in monkeys with more severe parkinsonism. We next determined how nicotine's ability to reduce LIDs correlated with lesion-induced changes in the striatal dopamine transporter and 3H-dopamine release in these two groups of monkeys. The striatal dopamine transporter was reduced to 54% and 28% of control in mild-moderately and more severely parkinsonian monkeys, respectively. However, basal, K+, α4β2 and α6β2 nAChR-evoked 3H-dopamine release were near control levels in striatum of mild-moderately parkinsonian monkeys. By contrast, these same release measures were reduced to a significantly greater extent in striatum of more severely parkinsonian monkeys. Thus, nicotine best improves LIDs in lesioned monkeys in which striatal dopamine transmission is still relatively intact. These data suggest that nicotine treatment would most effectively reduce LIDs in patients with mild to moderate Parkinson's disease.
机译：l-多巴诱发的运动障碍（LIDs）是异常的非自愿运动，随着帕金森氏病的长期l-多巴疗法的发展而发展。研究表明，在几种帕金森病动物模型中，尼古丁给药可降低LID。目前的工作是为了了解调节MPTP损伤的非人类灵长类动物中尼古丁介导的LID减少的调控因素。为了解决这个问题，我们使用了两组猴子，一组为中度-中度，另一组为更严重的帕金森综合症，使用左旋多巴导致运动障碍。在轻度-中度帕金森病猴子中，尼古丁预处理（通过饮用水300μg/ ml）可防止LID发生约75％。当尼古丁剂量降低至50μg/ ml时，这种改善得以保持，但由于尼古丁去除而失去了。尼古丁再接触再次降低了LID。相比之下，尼古丁治疗并不能减轻帕金森病更为严重的猴子的LID。接下来，我们确定了这两组猴子中尼古丁减少LID的能力与病变引起的纹状体多巴胺转运蛋白变化和3H-多巴胺释放如何相关。在轻度中度和重度帕金森病猴中，纹状体多巴胺转运蛋白分别降低至对照组的54％和28％。然而，基础，K +，α4β2和α6β2nAChR诱发的3H-多巴胺释放在轻度-中度帕金森病猴纹状体中接近于对照水平。相比之下，在更严重的帕金森病猴的纹状体中，这些相同的释放措施明显降低。因此，尼古丁最能改善纹状体多巴胺传递仍相对完整的患病猴子的LID。这些数据表明，尼古丁治疗将最有效地减轻轻度至中度帕金森氏病患者的LID。

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