INCREASED SENSITIVITY OF THE HIPPOCAMPUS IN ETHANOL-DEPENDENT RATS TO TOXIC EFFECT OF N-METHYL-D-ASPARTIC ACID INVIVO
INCREASED SENSITIVITY OF THE HIPPOCAMPUS IN ETHANOL-DEPENDENT RATS TO TOXIC EFFECT OF N-METHYL-D-ASPARTIC ACID INVIVO
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DOI：
10.1016/0006-8993(93)91562-7
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发表时间：
1993-03-19
期刊：
影响因子：
2.9
通讯作者：
SHANLEY, BC
中科院分区：
文献类型：
--
作者：
DAVIDSON, MD;WILCE, P;SHANLEY, BC
在动物中长期给予乙醇导致CNS耐受性和身体依赖性。随后的乙醇戒断导致过度兴奋，这被认为与N-甲基-D-天冬氨酸（NMDA）受体的敏感性增加有关。本研究的目的是通过检测海马内注射NMDA后的损伤来研究乙醇处理的动物对NMDA的敏感性。胆碱乙酰转移酶（ChAT）和谷氨酸脱羧酶（GAD）的比活性分别作为胆碱能和γ-氨基丁酸神经元的标记物。海马内注射120或240 nmol NMDA后，乙醇依赖性动物更容易死亡。在存活的动物中，海马GAD的下降幅度更大，但ChAT的比活性没有下降。这些数据支持了乙醇依赖与NMDA敏感性增加相关的假设，NMDA可能是兴奋性毒性脑损伤和死亡的原因。
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.