Davidson M D, Wilce P, Shanley B C
Department of Biochemistry, University of Queensland, Australia.
Brain Res. 1993 Mar 19;606(1):5-9. doi: 10.1016/0006-8993(93)91562-7.
Chronic administration of ethanol in animals leads to CNS tolerance and physical dependence. Subsequent withdrawal of ethanol causes hyperexcitability which is thought to be related to increased sensitivity of N-methyl-D-aspartic acid (NMDA) receptors. The purpose of this study was to investigate sensitivity to NMDA in ethanol-treated animals by detecting damage after intrahippocampal injection of NMDA. Choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) specific activity was used as markers of cholinergic and gamma-aminobutyric acid neurons, respectively. Ethanol-dependent animals were more liable to die following intrahippocampal injection of either 120 or 240 nmol of NMDA. There was a significantly greater decrease in hippocampal GAD but not ChAT specific activity in the surviving animals. These data support the hypothesis that ethanol dependence is associated with increased sensitivity to NMDA which may be responsible for excitotoxic brain damage and death.
在动物中长期给予乙醇会导致中枢神经系统耐受和身体依赖。随后停止给予乙醇会引发过度兴奋，这被认为与N-甲基-D-天冬氨酸（NMDA）受体敏感性增加有关。本研究的目的是通过检测海马内注射NMDA后的损伤情况，来研究乙醇处理动物对NMDA的敏感性。胆碱乙酰转移酶（ChAT）和谷氨酸脱羧酶（GAD）的比活性分别用作胆碱能神经元和γ-氨基丁酸神经元的标志物。海马内注射120或240 nmol的NMDA后，乙醇依赖动物更易死亡。在存活的动物中，海马GAD比活性显著降低，但ChAT比活性未降低。这些数据支持了以下假设：乙醇依赖与对NMDA敏感性增加有关，这可能是导致兴奋性毒性脑损伤和死亡的原因。
