Influence of corticostriatal δ-opioid receptors on abnormal involuntary movements induced by L-DOPA in hemiparkinsonian rats
Influence of corticostriatal δ-opioid receptors on abnormal involuntary movements induced by L-DOPA in hemiparkinsonian rats
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DOI：
10.1016/j.expneurol.2012.04.017
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发表时间：
2012-08-01
影响因子：
5.3
通讯作者：
Dourmap, Nathalie
中科院分区：
文献类型：
--
作者：
Billet, Fabrice;Costentin, Jean;Dourmap, Nathalie
帕金森病的长期L-3，4-二羟基苯丙氨酸（L-DOPA）治疗及时诱导许多副作用，例如称为L-DOPA诱导的运动障碍（LID）的异常不自主运动。已经假设纹状体输出通路中的谷氨酸传输、多巴胺传输和阿片样物质传输参与LIDS的诱导。有趣的是，我们以前的实验表明，一些纹状体δ-阿片受体位于纹状体能皮质纹状体神经元的末端，刺激这些受体调节谷氨酸和多巴胺的释放。本研究进行测试的参与δ-阿片受体，更准确地说，那些位于皮质纹状体神经元，在异常不自主运动引起的左旋多巴在偏侧帕金森病大鼠。在皮质纹状体去传入或未去传入的动物中，研究了δ阿片受体的选择性激动剂[D-Pen（2），D-Pen（5）]-脑啡肽（DPDPE）和选择性拮抗剂（纳曲吲哚）对LID的影响。我们的研究结果表明，DPDPE和纳曲吲哚分别增强和减少LIDS的动物，其中同侧皮层保存完好。然而，同侧皮质的损伤阻止了DPDPE对LIDS的刺激作用。还研究了[H-3]-DPDPE与从整个纹状体制备的纹状体膜的结合。与非运动障碍动物相比，在运动障碍动物的纹状体中发现δ-阿片受体的密度显著增加，但这种差异被皮质纹状体传入阻滞所消除。这些结果表明，δ-阿片传递调节啮齿类动物的LIDS的表达，并建议，δ-阿片受体参与这种效果位于皮质纹状体神经元的终端。(C)2012 Elsevier Inc. All rights reserved.
Chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment of Parkinson's disease induces in time numerous side effects, such as abnormal involuntary movements called L-DOPA-induced dyskinesias (LIDs). An involvement of glutamate transmission, dopamine transmission and opioid transmission in striatal output pathways has been hypothesized for the induction of LIDs. Interestingly, our previous experiments indicated that some striatal delta-opioid receptors are located on terminals of glutamatergic corticostriatal neurons and that stimulation of these receptors modulates the release of glutamate and dopamine. The present study was performed to test the involvement of delta-opioid receptors, and more precisely of those located on corticostriatal neurons, in abnormal involuntary movements induced by L-DOPA in hemiparkinsonian rats. The effects of a selective agonist, [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE) and a selective antagonist (naltrindole) of delta-opioid receptors on LIDs were investigated in animals submitted or not to a corticostriatal deafferentation. Our results indicate that DPDPE and naltrindole respectively enhanced and reduced LIDs in animals in which the ipsilateral cortex was preserved intact. However, the lesion of the ipsilateral cortex prevented the stimulant effect of DPDPE on LIDs. The [H-3]-DPDPE binding to striatal membranes prepared from the whole striatum was also studied. A significant increase in density of delta-opioid receptors was found in the striatum of dyskinetic animals as compared to non-dyskinetic animals but this difference was abolished by the corticostriatal deafferentation. These results indicate that delta-opioid transmission modulates the expression of LIDs in rodents and suggest that the delta-opioid receptors involved in this effect are located on terminals of corticostriatal neurons. (C) 2012 Elsevier Inc. All rights reserved.