Interactions of serotonin receptors and ethanol in the rat brain slice

Abstract

Alcoholism, which is characterized by chronic ethanol abuse, has caused enormous social and health problems. Investigation into the mechanism of ethanol intoxication should provide useful information for treatment and prevention of alcohol abuse. Research evidence indicates that the central serotonergic (5HT) system is involved in the mechanism of ethanol intoxication. Ethanol preference (the desire to drink ethanol) is consistently inhibited by increases in central serotonergic tone. But the specific site or mechanism of interaction between the central serotonergic system and ethanol is not clear. In this project, intracellular electrophysiological methods were used to investigate whether serotonergic receptor-mediated functional activity interacts with ethanol. Serotonin receptors mediate several cellular electrophysiological actions, some of which are affected by ethanol. The findings of this project indicate that neither acute ethanol treatment in vitro nor chronic ethanol treatment in vivo affected 5HT[1A] receptor-mediated hyperpolarization responses in the hippocampal CA1 region of the rat. 5HT receptor-mediated blockade of the after-hyperpolarization (AHP) following a burst of action potentials in rat hippocampal CA1 neurons, an intrinsic and ubiquitous inhibitory mechanism in the CNS, was enhanced during a prolonged (>30 min) application of an intoxicating concentration of ethanol (30 mM). However, the effect of a shorter (5 min) application of ethanol on the 5HT receptor-mediated AHP blockade was marginal. The AHP was augmented by 43 % during acute ethanol treatment (30 mM), which was the most dramatic effect of ethanol observed at the cellular level. These results suggest that ethanol may indirectly affect 5HT receptor-mediated AHP blockade. In another study, ethanol dependence did not affect 5HT receptor-mediated AHP blockade. At present, it is not clear how this action may contribute to the mechanism of ethanol intoxication. Overall the present findings suggest that the function of 5HT receptors in the hippocampus is not dramatically altered by acute or chronic ethanol treatment.