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Journal of Neuroscience, Vol 10, 1372-1379, Copyright © 1990 by Society for Neuroscience
NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat
DM Lovinger, G White and FF Weight
Section of Electrophysiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852.
The effect of ethanol (EtOH) on synaptic transmission mediated by N-
methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors was investigated
in slices from adult rat hippocampus. Synaptic responses were elicited by
stimulation of stratum radiatum and were recorded in CA1 stratum radiatum
or stratum pyramidale. Population EPSPs (pEPSPs) mediated by NMDA receptor
activation were isolated by application of a solution containing the
kainate/quisqualate receptor antagonist 6,7- dinitroquinoxaline-2,3-dione
and either low (0.1 mM) Mg2+ or 100 microM bicuculline. Increasing
concentrations of EtOH produced increasing inhibition of NMDA
receptor-mediated pEPSPs with EtOH concentrations between 1 and 50 mM. At a
concentration of 50 mM, EtOH inhibited NMDA receptor-mediated pEPSPS by
43%; the inhibition by 100 mM EtOH was not significantly different from
that produced by 50 mM. Methanol and 1- butanol also inhibited the NMDA
receptor-mediated pEPSPs; the potency of the alcohols for inhibition of
NMDA receptor-mediated pEPSPs was 1- butanol greater than ethanol greater
than methanol. pEPSPs mediated by non-NMDA glutamate receptors were
isolated by the application of the NMDA receptor antagonist
d,1-2-amino-5-phosphonovaleric acid in the presence of 1.5 mM Mg2+. These
pEPSPs were not significantly affected by 50 mM EtOH, whereas 100 mM EtOH
reduced the amplitude of these pEPSPs by 9%. The observations indicate that
synaptic excitation mediated by NMDA receptors in tissue from adult rat is
inhibited by intoxicating concentrations of EtOH. The data are consistent
with the hypothesis that EtOH-induced inhibition of EPSPs mediated NMDA
receptors may contribute to the intoxicating effects of EtOH.
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