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Pharmacological and molecular mechanism on amino acid neural transmission in brain of animal model for drug abuse

药物滥用动物模型脑内氨基酸神经传递的药理学和分子机制

基本信息

批准号：
12670924
负责人：
SUZUKI Toshihito
金额：
$ 2.18万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670924/
关键词：
cocaine phencyclidine glutamate GABA receptor subunit behavioral sensitization drug abuse Drug abuse Cocaine NMDA receptor GABAB receptor Benzo diazepine Receptor subunit in situ hybridization

项目摘要

Chronic use of cocaine or phencyclidine can result in the induction of a psychotic state resembling paranoid schizophrenia. Behavioral sensitization resulting from repeated administration of cocaine has been well documented in animal experiments. While dopaminergic systems may be responsible for the development of sensitization, glutamatergic or GABAergic neural system also influences these behavioral abnormalities. We investigated the effects of intraperitoneal administration of cocaine or phencyclidine on the mRNA levels of ionotropic or metabotropic glutamate receptor and GABA receptor subunits in rat brain. As a result, (1) The amount of the NR1 subunit mRNA of the NMDA receptor significantly increased in the hippocampus following a single administration of cocaine (20 mg/kg). Chronic cocaine administration caused a reduction in the level of NR1 subunit mRNA in the striatum and an increase in the hippocampus. (2) A level of α1, β2, β3, γ2 subunit of GABA-benzodiazepine complex was decreased in the cortex and hippocampus following a single injection of cocaine. In chronically treated rats, the level of β3 subunit of GABA-BZD receptor was significantly reduced in the cortex and caudate-putamen. In addition, the nucleus accumbens, hippocampus and thalamus showed a significant increase in the level of GABAB(1) mRNA following repeated administration of cocaine. (3) After repeated phencyclidine administration, mGluR2 and mGluR4 mRNA expression was significantly decreased in the cortex, while a single administration resulted in a decrease in the mGluR mRNA in the cortex. These findings suggested that single and repeated administration of cocaine and phencyclidine independently regulate the mRNA expression of subunits of glutamate and GABA-BZD receptors in the brain.

长期使用可卡因或苯环己哌啶可导致类似偏执型精神分裂症的精神病状态。动物实验中已充分记录了重复施用可卡因导致的行为过敏。虽然多巴胺能系统可能负责致敏的发生，但谷氨酸能或 GABA 能神经系统也会影响这些行为异常。我们研究了腹腔注射可卡因或苯环己哌啶对大鼠脑中离子型或代谢型谷氨酸受体和 GABA 受体亚基 mRNA 水平的影响。结果，(1)单次给予可卡因(20mg/kg)后，海马中NMDA受体的NR1亚基mRNA的量显着增加。长期服用可卡因会导致纹状体中 NR1 亚基 mRNA 水平降低，而海马体中 NR1 亚基 mRNA 水平增加。 (2)单次注射可卡因后，皮层和海马中GABA-苯二氮卓复合物的α1、β2、β3、γ2亚基水平降低。在长期治疗的大鼠中，皮质和尾壳核中 GABA-BZD 受体 β3 亚基的水平显着降低。此外，重复给予可卡因后，伏核、海马和丘脑的 GABAB(1) mRNA 水平显着增加。 (3)重复给予苯环己哌啶后，皮质中mGluR2和mGluR4 mRNA表达显着降低，而单次给药导致皮质中mGluR mRNA表达降低。这些发现表明，单次和重复施用可卡因和苯环己哌啶可独立调节大脑中谷氨酸和 GABA-BZD 受体亚基的 mRNA 表达。