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The changes of neurotransmitters and cellular reactions in the rats with methamphetamine injection

注射甲基苯丙胺大鼠神经递质及细胞反应的变化

基本信息

批准号：
11670417
负责人：
TAKAHASHI Setsunori
金额：
$ 2.43万
依托单位：
SHIMANE MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

To evaluate the time course changes of extracellular amino acid concentrations in the rat striatum and hippocampus, methamphetamine injection combined with an in vivo brain microdialysis technique was applied. After the injection of methamphetamine, extracellular glutamate and dopamine levels were significantly increased in striatum and hippocampus. However, the elevation of glutamate level was almost the same to saline injection cases. The elevation of dopamine level was several to hundred times as compared to saline injection cases. The changes of dopamine levels was much greater in striatum than in hippocampus. The peculiar neurological and psychiatric manifestations were also observed in the cases of rats injected by methamphetamine. Our results suggest that these clinical symptoms were due to the rapid increasing of extracellular dopamine level in striatum, not glutamate.Histopathological examinations were performed in the brain tissues of rats injected methamphetamine. Morphologically, significant changes were not observed. However, immunohistochemical staining revealed that HSP-72 showed positive reaction in some glial cells in striatum. These results suggested that methamphetamine was closely related to the signal transduction systems in the cerebrum.In human autopsy case who died strongly suspected due to the methamphetamine addiction, marked fragmentations of muscle fibers were observed in the heart muscle by histological examination. HSP-72 was also detected in some cardiac muscle fibers and cerebral glial cells by immunohistochemical staining. These results suggested that an certain effect to the heart muscle should be in methamphetamine injection cases.

为评价大鼠纹状体和海马区细胞外氨基酸浓度的时程变化，采用甲基苯丙胺注射结合活体脑微透析技术。注射甲基苯丙胺后，纹状体和海马区细胞外谷氨酸和多巴胺水平显著升高。然而，谷氨酸水平的升高与生理盐水注射的情况几乎相同。与生理盐水注射病例相比，多巴胺水平升高了几到几百倍。纹状体多巴胺水平的变化明显大于海马区。在注射甲基苯丙胺的大鼠中也观察到了特殊的神经和精神症状。我们的结果表明，这些临床症状是由于纹状体内细胞外多巴胺水平的迅速增加，而不是谷氨酸。形态观察未见明显变化。免疫组织化学染色显示HSP-72在纹状体内部分神经胶质细胞呈阳性反应。这些结果表明，甲基苯丙胺与大脑中的信号转导系统密切相关。在疑似死于甲基苯丙胺成瘾的人类尸检病例中，组织学检查发现心肌中有明显的肌肉纤维断裂。免疫组织化学染色显示部分心肌纤维和脑胶质细胞表达HSP-72。提示甲基苯丙胺注射对心肌有一定影响。