Brain regional differences in glycine reversal of ethanol-induced inhibition of N-methyl-D-aspartate-stimulated neurotransmitter release.

Abstract

The present study investigated the interaction between glycine and ethanol on N-methyl-D-aspartate (NMDA)-stimulated neurotransmitter release in hippocampal, cerebrocortical, and striatal slices from rat brain. Some, but not all, previous studies have shown that glycine may reverse the inhibitory effect of ethanol on NMDA receptors. Hippocampal or cortical slices were prepared and prelabelled with [3H]norepinephrine, and striatal slices were labelled with [3H]dopamine. Stimulation of the slices with 500 microM NMDA for two minutes caused a significant release of [3H]neurotransmitter in each brain region above basal. Ethanol (60 mM) significantly inhibited the NMDA-stimulated release of neurotransmitter from all brain regions. Addition of glycine (0.3-3 microM) to the buffer bathing the slices had no effect on the inhibitory effect of ethanol in hippocampus or cortex. However, in striatal slices, 0.3 and 1.0 microM glycine added to the buffer reversed the inhibitory effect of ethanol on NMDA-stimulated [3H]dopamine release without having any effect on either basal or NMDA-stimulated release by itself. These results show that the interaction between ethanol and glycine varies in different brain regions. Therefore interpretation of the potential inhibitory effect of ethanol on NMDA receptor function in vivo should consider brain region and local concentrations of glycine.