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多巴胺D2样受体直接调节正常及帕金森病模型大鼠苍白球神经元自发放电

朱永村, 薛雁, 刁汇玲, 陈桦, 刘红云, 韩晓华, 陈蕾

青岛大学医学院1生理学教研室；附属市立医院病理科，青岛 266071

摘要

苍白球是基底神经节间接环路的重要核团，在机体正常及病理状态下调节运动功能。前期研究工作显示苍白球接受来自黑质纹状体轴突侧支的多巴胺能纤维支配。苍白球表达多巴胺D1和D2样受体。本研究旨在采用多管微电极细胞外电生理记录技术，探讨多巴胺D2样受体对正常及帕金森病模型大鼠苍白球神经元自发放电的直接调控效应。结果显示，在正常大鼠上，微压力给予多巴胺D2样受体激动剂quinpirole对苍白球神经元自发放电发挥不同的电生理效应。在所记录的61个苍白球神经元，quinpirole可使24个神经元的放电频率增加(62.7 ± 11.2)%，而使另外16个神经元放电频率降低(37.5 ± 2.9)%，联合给予D2样受体阻断剂sulpride可阻断quinpirole对苍白球神经元自发放电的调控效应。在6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)帕金森病模型大鼠损毁侧所记录的47个苍白球神经元中，quinpirole可使其中25个神经元的放电频率增加(64.2 ± 10.1)%，而使另外11个神经元放电频率降低(51.9 ± 6.2)%。以上结果提示，多巴胺D2样受体双向调节苍白球神经元的自发放电活动；在帕金森病状态下，多巴胺D2样受体仍具有双向调节苍白球神经元兴奋性的效应。

关键词： 苍白球; 多巴胺D2样受体; 帕金森病

分类号：R338

Direct modulation of firing activity by dopamine D2 like receptors in the globus pallidus of both normal and parkinsonian rats

ZHU Yong-Cun, XUE Yan, DIAO Hui-Ling, CHEN Hua, LIU Hong-Yun, HAN XIAO-HUA, CHEN Lei

Department of Physiology； Department of Pathology in Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266071, China

Abstract

he globus pallidus occupies a critical position in the indirect pathway of the basal ganglia circuit, which regulates movement under both normal and pathological conditions. Previous studies have shown that the globus pallidus receives dopaminergic innervation from the axonal collaterals of nigrostriatal fibers. Both dopamine D1 and D2 like receptors are expressed in the globus pallidus. The present study was aimed to investigate the direct in vivo electrophysiological effects of dopamine D2 like receptors in the globus pallidus of both normal and parkinsonian rats. Extracellular recordings of multi-barreled microelectrode were used in the present study. In normal rats, micro-pressure ejection of dopamine D2 like receptor agonist quinpirole induced different effects on the firing rate of globus pallidus neurons. In 24 out of the 61 pallidal neurons, quinpirole significantly increased the firing rate by (62.7 ± 11.2)%. In another 16 neurons, quinpirole decreased the spontaneous firing rate by (37.5 ± 2.9)%. Furthermore, co-application of dopamine D2 like receptor antagonist, sulpride, blocked quinpirole-induced modulation of the firing rate of pallidal neurons. On the 6- hydroxydopamine (6-OHDA) lesioned side of parkinsonian rats, quinpirole increased the firing rate in 25 out of the 47 pallidal neurons by (64.2 ± 10.1)%, while decreased the firing rate in 11 neurons by (51.9 ± 6.2)%. Our findings suggest that activation of pallidal dopamine D2 like receptors may bidirectionally modulate the spontaneous firing of globus pallidus neurons in both normal and parkinsonian rats.

Key words: Globus pallidus; dopamine D2 like receptors; Parkinson’s disease

收稿日期：2016-02-24　　录用日期：2016-08-23

通讯作者：陈蕾　　E-mail: chenleiqd@163.com

引用本文：

朱永村, 薛雁, 刁汇玲, 陈桦, 刘红云, 韩晓华, 陈蕾. 多巴胺D2样受体直接调节正常及帕金森病模型大鼠苍白球神经元自发放电[J]. 生理学报 2016; 68 (5): 699-707.

ZHU Yong-Cun, XUE Yan, DIAO Hui-Ling, CHEN Hua, LIU Hong-Yun, HAN XIAO-HUA, CHEN Lei. Direct modulation of firing activity by dopamine D2 like receptors in the globus pallidus of both normal and parkinsonian rats. Acta Physiol Sin 2016; 68 (5): 699-707 (in Chinese with English abstract).