Ethanol potentiates ion current mediated by 5-HT3 receptors on neuroblastoma cells and isolated neurons

Effects of ethanol on receptor/channel complexes appear to play an important role in acute intoxication. One such receptor that has not previously been investigated for ethanol sensitivity is the 5-HT3 receptor for the neurotransmitter serotonin. Ethanol potentiates ion current mediated by 5-HT3 receptors in NCB-20 neuroblastoma cells and isolated Nodose ganglion neurons examined with whole-cell patch-clamp recording. Potentiation increases in a concentration-dependent manner over a range of concentrations (25-100 mM) achieved during acute intoxication. Potentiation appears to be due to a direct effect on the 5-HT3 receptor. Ethanol's effect on 5-HT3 receptor-mediated current decreases with increasing agonist concentration, providing an initial clue as to the mechanism of ethanol's action. These data are discussed in light of recent behavioral data suggesting a role for 5-HT3 receptors in the discriminative stimulus and reinforcing properties of ethanol.