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.
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Y
Y
Wang
C H
CH
Jeng
J C
JC
Lin
J Y
JY
Wang
D000818:Animals; D003864:Depression, Chemical; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*
D011985:Receptors, Serotonin; D012701:Serotonin; D000431:Ethanol