INCREASED NMDA-INDUCED EXCITABILITY DURING ETHANOL WITHDRAWAL - A BEHAVIORAL AND HISTOLOGICAL STUDY

被引:79
作者
DAVIDSON, M
SHANLEY, B
WILCE, P
机构
[1] Alcohol Research Unit, Department of Biochemistry, University of Queensland
基金
英国医学研究理事会;
关键词
N-METHYL-D-ASPARTATE; ETHANOL; RAT HIPPOCAMPUS; ALCOHOL WITHDRAWAL; EXCITOTOXICITY;
D O I
10.1016/0006-8993(94)01440-S
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 Using control and ethanol-withdrawn male Wistar rats, behavioural indices were determined immediately after injection and morphological damage was assessed after a period of recovery.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.
引用
收藏
页码:91 / 96
页数:6
相关论文
共 36 条
  • [1] AHERN KV, 1994, NEUROSCI LETT, V165, P211
  • [2] KINDLING AS A MODEL FOR ALCOHOL WITHDRAWAL SYNDROMES
    BALLENGER, JC
    POST, RM
    [J]. BRITISH JOURNAL OF PSYCHIATRY, 1978, 133 (JUL) : 1 - 14
  • [3] CHRONIC ETHANOL EXPOSURE POTENTIATES NMDA EXCITOTOXICITY IN CEREBRAL CORTICAL-NEURONS
    CHANDLER, LJ
    NEWSOM, H
    SUMNERS, C
    CREWS, F
    [J]. JOURNAL OF NEUROCHEMISTRY, 1993, 60 (04) : 1578 - 1581
  • [4] ETHANOL INHIBITS NMDA RECEPTOR-MEDIATED EXCITOTOXICITY IN RAT PRIMARY NEURONAL CULTURES
    CHANDLER, LJ
    SUMNERS, C
    CREWS, FT
    [J]. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1993, 17 (01) : 54 - 60
  • [5] THE INVOLVEMENT OF NMDA RECEPTORS IN ACUTE AND CHRONIC EFFECTS OF ETHANOL
    DANYSZ, W
    DYR, W
    JANKOWSKA, E
    GLAZEWSKI, S
    KOSTOWSKI, W
    [J]. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1992, 16 (03) : 499 - 504
  • [6] INCREASED SENSITIVITY OF THE HIPPOCAMPUS IN ETHANOL-DEPENDENT RATS TO TOXIC EFFECT OF N-METHYL-D-ASPARTIC ACID INVIVO
    DAVIDSON, MD
    WILCE, P
    SHANLEY, BC
    [J]. BRAIN RESEARCH, 1993, 606 (01) : 5 - 9
  • [7] ETHANOL INHIBITS NMDA-INDUCED INCREASES IN FREE INTRACELLULAR CA-2+ IN DISSOCIATED BRAIN-CELLS
    DILDY, JE
    LESLIE, SW
    [J]. BRAIN RESEARCH, 1989, 499 (02) : 383 - 387
  • [8] INHIBITION OF N-METHYL-D-ASPARTATE-INDUCED NORADRENALINE RELEASE BY ALCOHOLS IS RELATED TO THEIR HYDROPHOBICITY
    FINK, K
    GOTHERT, M
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 191 (02) : 225 - 229
  • [9] GONZALES RA, 1990, J PHARMACOL EXP THER, V253, P1138
  • [10] ETHANOL WITHDRAWAL SEIZURES AND THE NMDA RECEPTOR COMPLEX
    GRANT, KA
    VALVERIUS, P
    HUDSPITH, M
    TABAKOFF, B
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 176 (03) : 289 - 296