Inhibition of N-methyl-D-aspartate (NMDA)- and L-glutamate-induced noradrenaline and acetylcholine release in the rat brain by ethanol.

The influence of ethanol on stimulation-evoked 3H-transmitter release was examined in slices of the rat brain cortex and corpus striatum preincubated with 3H-noradrenaline and 3H-choline, respectively. 3H-Transmitter release was stimulated by NMDA, L-glutamate, electrical impulses, reintroduction of Ca2+ ions ("Ca2(+)-evoked release", after superfusion with Ca2(+)-free, K(+)-rich solution) or veratridine. In cortical slices preincubated with 3H-noradrenaline and superfused with Mg2(+)-free, otherwise physiologically composed salt solution, ethanol inhibited the NMDA- or L-glutamate-induced tritium overflow (IC50 45 and 37 mmol/l, respectively). In contrast, the tritium overflow in response to electrical stimulation, reintroduction of Ca2+ ions or veratridine was not affected by ethanol at concentrations up to 320 mmol/l; these experiments were carried out in cortical slices superfused with solution containing a physiological Mg2+ concentration. Ethanol also failed to inhibit Ca2(+)-evoked release in the absence of Mg2+ ions. In the presence of 1 mumol/l veratridine, but not in its absence, NMDA induced tritium overflow even when cortical slices were superfused with salt solution containing a physiological Mg2+ concentration; again, ethanol inhibited this NMDA-evoked tritium overflow (IC50 73 mmol/l. In striatal slices preincubated with 3H-choline and superfused with Mg2(+)-free "physiological" salt solution the NMDA-evoked tritium overflow was also, although at lower potency, inhibited by ethanol (IC50 192 mmol/l). In spite of the differences between the IC50 values of ethanol determined for the inhibition of cortical noradrenaline and striatal acetylcholine release, it may be concluded that the NMDA receptor-ion channel complex is one of the sites of action underlying the ethanol-induced inhibition of neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)