Modulation of ethanol-induced inhibition of N-methyl-D-aspartate-stimulated neurotransmitter release by glycine.
N-methyl-D-aspartate (NMDA) stimulated a concentration dependent release of tritiated norepinephrine from cortical slices and tritiated and endogenous dopamine from striatal slices prepared from adult rat brain. Release of both neurotransmitters was abolished by tetrodotoxin, magnesium, and the NMDA specific antagonist, 2-amino-5-phosphonopentanoic acid (AP-5). Ethanol (60-200 mM) significantly decreased the release of [3H]-norepinephrine from cortical slices evoked by NMDA in a concentration-dependent manner (32-52%) without altering basal release. Similarly, ethanol (25-200 mM) markedly inhibited the NMDA stimulated release of tritiated and endogenous dopamine without affecting basal release. Glycine, in low micromolar concentrations reversed the inhibition of NMDA stimulated neurotransmitter release from cortical and striatal slices and in striatal slices shifted ethanol's inhibitory dose response curve to the right. These data suggest that alcohol may produce some of its effects in the brain by inhibiting the glutamate stimulated release of catecholamine neurotransmitters. These data also suggest that this inhibition may be mediated by altering or interfering with the glycine modulatory site on the NMDA receptor complex.
Woodward
J J
JJ
Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond 23298.
Brown
L
L
Gonzales
R A
RA
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005998:Glycine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D016202:N-Methylaspartate; D005998:Glycine; D004298:Dopamine; D009638:Norepinephrine