INCREASED NMDA-INDUCED EXCITABILITY DURING ETHANOL WITHDRAWAL - A BEHAVIORAL AND HISTOLOGICAL STUDY
INCREASED NMDA-INDUCED EXCITABILITY DURING ETHANOL WITHDRAWAL - A BEHAVIORAL AND HISTOLOGICAL STUDY
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DOI：
10.1016/0006-8993(94)01440-s
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发表时间：
1995-03-13
期刊：
影响因子：
2.9
通讯作者：
WILCE, P
中科院分区：
文献类型：
--
作者：
DAVIDSON, M;SHANLEY, B;WILCE, P
海马内注射N-甲基-D-天冬氨酸（NMDA）导致神经退行性变，呈剂量依赖性。对动物长期给予乙醇导致CNS耐受性和依赖性。乙醇戒断后的过度兴奋被认为与NMDA受体的敏感性增加有关。本研究的目的是通过海马内注射低剂量的NMDA来研究这种过度兴奋的倾向。使用对照组和戒断乙醇的雄性Wistar大鼠，注射后立即测定行为指数，恢复一段时间后评估形态学损伤。注射后立即在乙醇处理的大鼠中有显著增加的活动过度。5 nmol NMDA导致的形态学损伤在这些动物的海马CA 3区显著更大。这些数据支持这一假设，即乙醇依赖和随后的戒断与NMDA敏感性增加有关，这可能是乙醇戒断相关脑损伤的基础。
Intrahippocampal injections of N-methyl-D-aspartic acid (NMDA) leads to neurodegeneration in a dose-dependent manner. Chronic administration of ethanol to animals leads to CNS tolerance and dependence. Hyperexcitability following ethanol withdrawal is thought to be related to increased sensitivity of the NMDA receptors. The purpose of this study was to investigate this predisposition to hyperexcitability by intrahippocampal injection of low doses of NMDA. Using control and ethanol-withdrawn male Wistar rats, behavioural indices were determined immediately after injection and morphological damage was assessed after a period of recovery. There was significantly increased hyperactivity in the ethanol-treated rats immediately after injection. Morphological damage resulting from 5 nmol of NMDA was significantly greater in the CA3 region of the hippocampus in these animals. These data support the hypothesis that ethanol dependence and subsequent withdrawal is associated with increased sensitivity to NMDA which may underlie ethanol withdrawal-associated brain damage.