5-HT3 receptor over-expression enhances ethanol sensitivity in mice

Ethanol sensitivity may play a role in the risk of developing alcoholism. The role of 5-HT3 receptors in sensitivity to ethanol was assessed in mice over-expressing the 5-HT3 receptor in the forebrain. Sleep time and ED50 for loss of righting reflex (LRR) were used to assess the effect of a high dose of ethanol in transgenic versus non-transgenic mice. The ED50 for ethanol-induced increase in open field activity was used to measure differences in sensitivity to low dose ethanol. The ED50 for ethanol-induced increase in activity was 41% lower in the 5-HT3 receptor over-expressing transgenic mice compared to non-transgenic mice. However, 5-HT3 receptor over-expressing mice did not differ from control mice in ethanol metabolism, ED50 for LRR, and ethanol sleep time. Over-expression of 5-HT3 receptors in mouse forebrain results in an enhanced sensitivity to the stimulating effects of a low dose of ethanol without altering ethanol sedating effects or ethanol metabolism. These data suggest that 5-HT3 receptors modulate low dose ethanol sensitivity and may explain why, in previous studies, these mice consume less ethanol.