Quantitative Autoradiographic Study on Receptor Regulation in the Basal Ganglia in Rat Model of Levodopa-induced Motor Complications  

作　　者：徐岩 张振涛 秦开蓉 Stella M.Papa 曹学兵 

机构地区：[1]Department of Neurology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology [2]Department of Rehabilitation,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology [3]Department of Neurology,School of Medicine,Emory University

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2009年第2期156-162,共7页华中科技大学学报（医学英德文版）

基　　金：supported by a grant from the National Natural Science Foundation of China (No.30770753)

摘　　要：In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications, quantitative autoradiography was used to observe receptor bindings of dopamine D1 and D2, N-methyl-D-aspartate （NMDA）, amino-3-hydroxy-5-methylisoxazole propionic acid （AMPA） and amino butyric acid （GABA） in the basal ganglia of rats that had unilateral nigrostriatal lesions and had been chronically treated with levodopa until motor complications developed. The rats were randomly assigned to three groups： normal, denervated and treatment-complicated groups. The results showed that response duration to levodopa became progressively shorter and abnormal involuntary movement （AIM） score was progressively increased during the course of levodopa treatment. Chronic treatment augmented D1 receptors more than denervation, and reduced D2 receptors that were also increased by dopamine denervation. Striatal NMDA receptors were substantially up-regulated in the treatment-complicated group. Levodopa treatment did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA, which remained the same as that in denervation group. However, chronic treatment reversed the increase of nigral GABA receptors caused by the lesion. It was concluded that a shortening of response duration and AIM mimicked levodopa-induced motor complications of Parkinson＇s patients. These data suggested that up-regulation of dopamine D1 and NMDA receptors in the striatum leads to an imbalance of stimulation through the striatal output pathways, which is associated with levodopa-induced motor complications.In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications, quantitative autoradiography was used to observe receptor bindings of dopamine D1 and D2, N-methyl-D-aspartate （NMDA）, amino-3-hydroxy-5-methylisoxazole propionic acid （AMPA） and amino butyric acid （GABA） in the basal ganglia of rats that had unilateral nigrostriatal lesions and had been chronically treated with levodopa until motor complications developed. The rats were randomly assigned to three groups： normal, denervated and treatment-complicated groups. The results showed that response duration to levodopa became progressively shorter and abnormal involuntary movement （AIM） score was progressively increased during the course of levodopa treatment. Chronic treatment augmented D1 receptors more than denervation, and reduced D2 receptors that were also increased by dopamine denervation. Striatal NMDA receptors were substantially up-regulated in the treatment-complicated group. Levodopa treatment did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA, which remained the same as that in denervation group. However, chronic treatment reversed the increase of nigral GABA receptors caused by the lesion. It was concluded that a shortening of response duration and AIM mimicked levodopa-induced motor complications of Parkinson＇s patients. These data suggested that up-regulation of dopamine D1 and NMDA receptors in the striatum leads to an imbalance of stimulation through the striatal output pathways, which is associated with levodopa-induced motor complications.

关 键 词：levodopa-induced motor complications Parkinson＇s disease glutamate receptors GABA receptors dopaminc receptors AUTORADIOGRAPHY 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]