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单侧多巴胺耗竭后纹状体中多巴胺受体的不对称变化。

Asymmetrical changes of dopamine receptors in the striatum after unilateral dopamine depletion.

作者信息

Xu Zao C, Ling Guangyi, Sahr Robert N, Neal-Beliveau Bethany S

机构信息

Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 507, Indianapolis, IN 46202, USA.

出版信息

Brain Res. 2005 Mar 21;1038(2):163-70. doi: 10.1016/j.brainres.2005.01.033.

Abstract

Dopamine plays an important role in modulating synaptic transmission in the striatum and has great influence on the function of the basal ganglia. Degeneration of dopamine neurons in the substantia nigra (SN) is the major cause of many neurological disorders, and the reduction of dopamine innervation results in alterations of dopamine receptors in the striatum. It has been shown that the nigrostriatal dopamine system has functional and neurochemical asymmetry. To investigate the lateralization of dopamine receptors in the striatum after dopamine denervation, the present study used quantitative autoradiography to compare the changes in dopamine receptor binding in the left and right striatum in rats after unilateral dopamine depletion. In comparison to control levels, dopamine D1)-like receptor binding, labeled with [3H]-SCH23390, in the dorsal striatum was reduced 2 weeks after unilateral lesions of the SN with 6-hydroxydopamine. D1-like receptor binding was decreased in the ipsilateral striatum following unilateral lesions of either the left or right SN. The left and right striatum responded similarly to unilateral SN lesions, as there were no significant differences in the percent decrease in D1-like binding in the two striata. In contrast, D2-like receptor binding, labeled with [3H]-spiroperidol, was significantly increased in the dorsal striatum following an ipsilateral SN lesion. Furthermore, the up-regulation of D2-like receptors in the right striatum was significantly greater than that in the left striatum after an ipsilateral lesion. The asymmetrical up-regulation of striatal D2 receptors after extensive dopamine depletion might contribute to the lateralization of the nigrostriatal system observed in some pathological conditions.

摘要

多巴胺在调节纹状体的突触传递中发挥着重要作用,并且对基底神经节的功能有很大影响。黑质(SN)中多巴胺神经元的退化是许多神经疾病的主要原因,多巴胺神经支配的减少会导致纹状体中多巴胺受体的改变。已有研究表明,黑质纹状体多巴胺系统存在功能和神经化学上的不对称性。为了研究多巴胺去神经支配后纹状体中多巴胺受体的偏侧化情况,本研究采用定量放射自显影术比较了单侧多巴胺耗竭后大鼠左右纹状体中多巴胺受体结合的变化。与对照水平相比,用[3H]-SCH23390标记的多巴胺D1样受体结合在单侧用6-羟基多巴胺损毁SN后2周,背侧纹状体中减少。单侧损毁左侧或右侧SN后,同侧纹状体中的D1样受体结合减少。左右纹状体对单侧SN损毁的反应相似,因为两个纹状体中D1样结合减少的百分比没有显著差异。相反,用[3H]-螺哌啶醇标记的D2样受体结合在同侧SN损毁后背侧纹状体中显著增加。此外,同侧损毁后右侧纹状体中D2样受体的上调明显大于左侧纹状体。广泛多巴胺耗竭后纹状体D2受体的不对称上调可能导致在某些病理情况下观察到的黑质纹状体系统的偏侧化。

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