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纹状体中 D1 和 D2 受体激动剂对运动活动和 GABA 水平的多巴胺能控制的差异。

Differential DAergic Control of D1 and D2 Receptor Agonist Over Locomotor Activity and GABA Level in the Striatum.

机构信息

Department of Basic Oriental Medical Science, Acupuncture & Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea.

出版信息

Exp Neurobiol. 2011 Sep;20(3):153-7. doi: 10.5607/en.2011.20.3.153. Epub 2011 Sep 20.

Abstract

The basal ganglia, a group of nuclei, are associated with a variety of functions, including motor control. The striatum, which is the major input station of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. The striatum is made up 96% of medium spiny neurons which are GABAergic cells. GABAergic cells are known to contain DA receptors which divide into two main branches- the D1 receptor (D1R)-expressing direct pathway and the D2 receptor (D2R)-expressing indirect pathway. The role of these two efferent pathways has not been clear in control of motor behaviors. To establish the influence of the different DA subtypes on GABAergic systems in the striatum, D1 selective receptor agonist (SKF 38393) and D2 selective receptor agonist (Quinpirole) were administered to mice. SKF 38393 and quinpirole were administered intraperitoneally in a volume of 0, 1, 5, 10 (mg/kg) and motor activity was assessed for 60 min immediately after the injection of DA agonists. Mice were sacrificed after behavioral test and the striatum in the brain were dissected for analysis of GABA level with HPLC. Both SKF 38393 and quinpirole dose-dependently increased locomotor activity but, GABA level in the striatum was clearly different in two agonists. These findings provide insight into the selective contributions of the direct and indirect pathways to striatal GABAergic motor behaviors.

摘要

基底神经节是一组核团,与多种功能有关,包括运动控制。纹状体是大脑中基底神经节的主要输入站,部分受到来自黑质的多巴胺能输入的调节。纹状体由 96%的中等棘突神经元组成,这些神经元是 GABA 能细胞。已知 GABA 能细胞含有多巴胺受体,这些受体分为两个主要分支——表达直接通路的 D1 受体(D1R)和表达间接通路的 D2 受体(D2R)。这两个传出通路在控制运动行为中的作用尚不清楚。为了确定不同 DA 亚型对纹状体 GABA 能系统的影响,向小鼠给予 D1 选择性受体激动剂(SKF 38393)和 D2 选择性受体激动剂(Quinpirole)。SKF 38393 和 quinpirole 以 0、1、5、10(mg/kg)的体积腹腔内给药,并在 DA 激动剂注射后立即进行 60 分钟的运动活动评估。行为测试后处死小鼠,取出大脑中的纹状体,用 HPLC 分析 GABA 水平。SKF 38393 和 quinpirole 均呈剂量依赖性地增加运动活性,但两种激动剂在纹状体中的 GABA 水平明显不同。这些发现为直接和间接通路对纹状体 GABA 能运动行为的选择性贡献提供了深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e1e/3214772/b3ae200f7bb4/en-20-153-g001.jpg

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