Ethanol withdrawal seizures and the NMDA receptor complex.
Prior biochemical and electrophysiological studies have shown that low doses of ethanol inhibited calcium influx through the N-methyl-D-aspartate (NMDA) receptor/ionophore. The present data show that chronic ethanol treatment results in an increase in the number of NMDA receptor/ionophore complexes in the hippocampus, a brain area known to be associated with ethanol withdrawal seizure activity. Treatment during withdrawal with NMDA-exacerbated handling induced withdrawal seizures in the ethanol-dependent mice, while administration of the NMDA receptor-associated calcium channel antagonist MK-801 decreased the occurrence and severity of the withdrawal seizures in a dose-dependent manner. The results are consistent with the hypothesis that the up-regulation of the NMDA receptor systems following chronic ethanol treatment may mediate the seizures associated with ethanol withdrawal in dependent animals.
Grant
K A
KA
Unit for Special Projects, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
Valverius
P
P
Hudspith
M
M
Tabakoff
B
B
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003986:Dibenzocycloheptenes / Q000378:metabolism / Q000494:pharmacology; D004032:Diet; D016291:Dizocilpine Maleate; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D000431:Ethanol; D016291:Dizocilpine Maleate