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MDMA神经毒性长期效应导致皮层和海马组织结构改变

李素霞, 李静, 王雪, 彭组贵, 况伟宏, 黄明生

四川大学基础与法医学院. 四川, 成都；四川大学华西医院心理卫生中心. 四川, 成都 610041

摘要

通过短时间多次给药建立3,4--亚甲基二氧基甲基苯丙胺(3,4--methylenedioxymethamphetamine , MDMA)的神经毒性模型，将雄性Wistar大鼠随机分为对照组和实验组，实验组给予MDMA 10 mg/kg，每小时一次，共4次，即总量为 40 mg/kg，对照组给予等体积生理盐水。于末次给药后32周采用原位杂交检测5--HT转运体(serotonin transporter, SERT) mRNA和内源性焦虑物质苯甲二氮结合性抑制物(diazepam binding inhibitor, DBI)的mRNA表达，免疫组织化学染色检测胶质纤维酸性蛋白(glial fibrillary acidic protein, GFAP)的表达，银染观察神经末梢变化。结果显示，短时间多次给予MDMA后，与生理盐水组比较，MDMA组大鼠海马SERT mRNA信号表达降低({sl P}<0.05)，大脑皮层DBI mRNA的信号表达增高({sl P}<0.05)，GFAP表达显著升高({sl P}<0.05); 银染MDMA组大鼠皮层神经末梢明显减少。上述结果提示，MDMA神经毒性导致皮层和海马结构改变持续存在，进而导致脑功能的紊乱。

关键词： MDMA; 神经毒性; 内源性焦虑物质; 5-HT转运体; 胶质纤维酸性蛋白; 神经末梢

Long--term neurotoxic effects of MDMA result in cortical and hippocampal structural changes

Li Suxia, Li Jing, Wang Xue, Peng Zugui, Kuang Weihong, Huang Mingsheng

Basic and Forensic School；Central of Psychology Health of West China Hospital, Sichuan University. Chengdu 610041, China

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) is a substituted amphetamine with stimulating and hallucinogenic properties. Since MDMA induces “ecstasy” it is extensively used as a “recreational”drug. It has been well established that MDMA is neurotoxic and can result in long-term degeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals in many species. The present study was undertaken to investigate the long-term neurotoxic effects of MDMA on cortical and hippocampal structures, by repeatedly administering MDMA in short time. Male Wistar rats were randomly assigned to control group and MDMA-treated group. MDMA (10 mg/kg) was administered to rats of MDMA-treated group, once per hour, total 40 mg/kg; rats of control group were treated with the same volume of saline. Thirty-two weeks after administering MDMA，the expression of serotonin transporter (SERT) mRNA and diazepam binding inhibitor (DBI) mRNA was detected by in situ hybridization. The expression of glial fibrillary acidic protein (GFAP) was detected by immunohistochemistry, and the degeneration of nerve terminals was demonstrated by Bielschowsky and Glee Marsland silver staining. The results showed that the expression of SERT mRNA in hippocampus decreased by 31.96%, while expression of DBI mRNA in neocortex increased by 40.51%, compared with the control group (P<0.05). The expression of GFAP in the brain tissue increased (P<0.05), while significant reduction of the nerve terminals in neocortex was demonstrated by silver staining, compared with the control group. These results suggest that the neurotoxicity of MDMA results in sustained cortical and hippocampal structural changes, which in turn result in disorder of the brain functions.

Key words: 3,4-methylenedioxymethamphetamine;Neurotoxicity;Diazepam binding inhibitor;Serotonin transporter;Glial fibrillary acidic protein;Nerve terminal

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引用本文：

李素霞, 李静, 王雪, 彭组贵, 况伟宏, 黄明生. MDMA神经毒性长期效应导致皮层和海马组织结构改变[J]. 生理学报 2006; 58 (1): .

Li Suxia, Li Jing, Wang Xue, Peng Zugui, Kuang Weihong, Huang Mingsheng. Long--term neurotoxic effects of MDMA result in cortical and hippocampal structural changes . Acta Physiol Sin 2006; 58 (1): (in Chinese with English abstract).