Interaction between N-methyl-D-aspartate (NMDA) and serotonin (5-HT) on ethanol tolerance

Earlier work from this laboratory had shown that 5-HT is involved in the development of tolerance to ethanol, and that enhancement of 5-HT levels by L-tryptophan accelerated tolerance development. To explore the possibility that NMDA receptors are involved in the 5-HT effect on tolerance, we examined the effect of a noncompetitive N-methyl-D-aspartate (NMDA) antagonist [(+)MK-801] on the ability of L-tryptophan to enhance tolerance to the effect of ethanol on tilt-plane test performance by the rat. L-Tryptophan treatment resulted in the development of rapid tolerance to a dose of ethanol that failed to produce such tolerance by itself. However, prior administration of (+)MK-801 blocked the L-tryptophan effect on rapid tolerance development, in a dose-dependent manner. These results suggest that NMDA receptors are involved in the 5-HT enhancement of ethanol tolerance.