Behavioral sensitization to different dopamine agonists in a parkinsonian rodent model of drug-induced dyskinesias
Behavioral sensitization to different dopamine agonists in a parkinsonian rodent model of drug-induced dyskinesias
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DOI：
10.1016/j.bbr.2003.10.009
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发表时间：
2004-07-09
影响因子：
2.7
通讯作者：
Gershanik, OS
中科院分区：
文献类型：
--
作者：
Delfino, MA;Stefano, AV;Gershanik, OS
多巴胺（DA）受体激动剂的重复治疗强烈增强对侧转向行为，由于选择性刺激D1或D2类受体在6-羟基多巴胺（6-OHDA）损伤的大鼠。这种现象被称为致敏，被认为与帕金森病患者长期服用左旋多巴期间发生的运动反应并发症（运动障碍，开关状态）有关。近年来，一种新的方法来评估异常不自主运动（AIM）继发于多巴胺能刺激在6-OHDA损毁大鼠。这些AIM类似于帕金森病患者在左旋多巴治疗下观察到的运动障碍。我们的目的是评估不同的DA受体激动剂的重复治疗对6-OHDA损伤大鼠的转向行为和AIMs量表的影响，目的是区分具有不同运动障碍诱导潜力的药物。此外，我们探讨了先前暴露于DA激动剂（引发）对随后施用具有相同或不同药理学特征的DA激动剂的行为反应的影响。我们的研究结果表明，在阿扑吗啡治疗的大鼠，旋转行为和AIM运行的增强平行的过程中，而在那些接收quinpirole有一个解离，这表明它们可以通过不同的机制介导。应牢记对6-OHDA损伤大鼠后续试验的显著引发效应的发现，因为在筛选损伤良好的动物时使用这些药理学试验可能导致对运动障碍和旋转行为的进一步结果的错误解释。(C)2003 Elsevier B. V.保留所有权利。
Repeated treatment with dopamine (DA) receptor agonists strongly potentiates contralateral turning behavior due to selective stimulation of D1 or D2-class receptors in 6-hydroxydopamine (6-OHDA)-lesioned rats. This phenomenon, referred to as sensitization, is believed to be related to the motor response complications (dyskinesias, on-off states) that occur during chronic administration of levodopa in Parkinson's disease patients. In recent years a new method for the evaluation of abnormal involuntary movements (AIMs) secondary to dopaminergic stimulation in 6-OHDA-lesioned rats was described. These AIMs resemble dyskinesias as seen in parkinsonian patients under levodopa therapy. Our objective was to evaluate the effects of repeated treatment with different regimes of DA agonists on turning behavior and on an AIMs scale in 6-OHDA lesioned rats, with the aim of discriminating between drugs with different dyskinesia-inducing potential. In addition, we explored the effects of a previous exposure to a DA agonist (priming) on the behavioral response to the subsequent administration of a DA agonist with the same or different pharmacologic profile. Our results show that in apomorphine-treated rats, rotational behavior and AIMs run a parallel course of enhancement, while in those receiving quinpirole there is a dissociation, suggesting that they could be mediated by different mechanisms. The finding of a significant priming effect on subsequent testing of 6-OHDA lesioned rats should be borne in mind as the use of these pharmacological tests in the screening of well lesioned animals could lead to an erroneous interpretation of further results on dyskinesias and rotational behavior. (C) 2003 Elsevier B.V. All rights reserved.