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

长期使用可卡因或苯环利定可导致类似偏执型精神分裂症的精神病状态。在动物实验中，多次服用可卡因导致的行为敏感化已经得到充分证明。虽然多巴胺能系统可能负责致敏的发展，但多巴胺能或GABA能神经系统也影响这些行为异常。我们研究了腹腔注射可卡因或苯环利定对大鼠脑内离子型或代谢型谷氨酸受体和GABA受体亚单位mRNA水平的影响。结果表明：（1）单次给予可卡因（20 mg/kg）后，海马中NMDA受体NR 1亚单位mRNA的量显著增加。慢性可卡因给药引起纹状体NR 1亚基mRNA水平降低和海马增加。(2)单次注射可卡因后，大脑皮层和海马GABA-苯二氮卓复合物α1、β2、β3、γ2亚单位的水平降低。在慢性处理的大鼠中，GABA-BZD受体β3亚单位的水平在皮质和尾壳核中显著降低。此外，重复给予可卡因后，丘脑、海马和丘脑的GABAB（1）mRNA水平显著增加。(3)苯环利定重复给药后，mGluR 2和mGluR 4的mRNA表达显着降低在皮层，而单次给药导致在皮层中的mGluR mRNA的减少。这些发现表明，单次和重复给药的可卡因和苯环利定独立调节谷氨酸和GABA-BZD受体的亚基在脑中的mRNA表达。

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.