Chronic ethanol administration sensitizes hippocampal neurons to neurotoxicity of N-methyl-D-aspartic acid.
The hyperexcitability observed following ethanol withdrawal in dependent animals is thought to be related to increased sensitivity of glutamate receptors. This may predispose to 'excitotoxic' neural damage. The aim of this study was to test this hypothesis by intrahippocampal injection of N-methyl-D-aspartic acid (NMDA) in ethanol-dependent rats and to quantify brain damage using enzymic neuronal markers, viz. choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD). Specific activity of GAD but not ChAT was found to be significantly decreased in hippocampi of ethanol-dependent animals following injection of NMDA, suggesting that chronic ethanol administration sensitizes GABAergic neurons to the toxic effects of excitatory amino acid transmitters.
Davidson
M
M
Department of Biochemistry, University of Queensland, St. Lucia, Australia.
Wilce
P A
PA
Shanley
B C
BC
D000437:Alcoholism / Q000201:enzymology; D000818:Animals; D015415:Biomarkers; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004351:Drug Resistance; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D000431:Ethanol; D016202:N-Methylaspartate; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase