Ethanol and magnesium ions inhibit N-methyl-D-aspartate-mediated synaptic potentials in an interactive manner.
The role of magnesium ions in the inhibitory effect of ethanol on NMDA receptor-mediated population synaptic potentials (pEPSPs) in area CA1 of the hippocampus of the adult rat, was studied. The excitatory amino acid (non-NMDA) receptor antagonist, DNQX and the GABAA channel antagonist, picrotoxin, were used to pharmacologically isolate NMDA-mediated pEPSPs. In the presence of a physiological concentration of magnesium (1.0 mM), ethanol (25-100 mM) inhibited NMDA-mediated pEPSPs, with an apparent EC50 of approximately 50 mM. The ability of ethanol to inhibit NMDA-mediated pEPSPs was reduced when the slices were incubated in the absence of magnesium. Concentrations of ethanol, in the range of 50-200 mM (apparent EC50 100 mM), were required to inhibit NMDA-mediated pEPSPs, in the absence of added magnesium. Combination studies of these two antagonists indicated that the sensitivity of NMDA-mediated pEPSPs to one antagonist was not altered by the presence of the other. This finding suggests that the affinity of each antagonist binding site is not affected by the presence of the other antagonist. In the case of ethanol, its low maximum antagonist efficacy may require larger concentrations of ethanol to inhibit NMDA-mediated pEPSPs, in the absence of other non-competitive antagonists such as magnesium.
Morrisett
R A
RA
Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710.
Martin
D
D
Oetting
T A
TA
Lewis
D V
DV
Wilson
W A
WA
Swartzwelder
H S
HS
D000818:Animals; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010852:Picrotoxin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013570:Synaptic Membranes / Q000187:drug effects*
D000431:Ethanol; D008274:Magnesium; D016202:N-Methylaspartate; D010852:Picrotoxin; D011810:Quinoxalines; C056723:FG 9041