Serotonin modulates ethanol-induced depression in cerebellar Purkinje neurons

In the present study, we found that local application of serotonin (5-HT) potentiated ethanol-induced depressions of the spontaneous activity of Purkinje neurons in urethane-anesthetized rats. 5-HT also potentiated depressions induced by gamma-aminobutyric acid; however, this modulatory response was quantitatively smaller than 5-HT-induced potentiation of ethanol depression. Previous reports suggested that the release of 5-HT can be regulated by presynaptic 5-HT autoreceptors. We found that local application of methiothepin, which may induce 5-HT overflow through the inhibition of presynaptic autoreceptors, facilitated ethanol-mediated responses. This methiothepin effect was greatly diminished in neonatally 5,7-dihydroxytryptamine-lesioned animals, suggesting a presynaptic mechanism was involved. We also found that the 5-HT1A antagonist UH301 did not attenuate 5-HT-facilitated ethanol reactions. On the other hand, local application of 5-HT1B agonist CGS12066B potentiated ethanol-induced depression. Taken together, our data suggest that 5-HT can modulate ethanol-mediated electrophysiological depression, possibly mediated through 5-HT1B receptors in the cerebellum.