Modulation of 5-HT 1C receptors and phosphoinositide system by ethanol consumption in rat brain and choroid plexus

Abstract

The effect of chronic ethanol consumption (60 days) on 5-HT 1C receptors as measured by [ 3H]mesulergine binding in the hippocampus, cortex, and choroid plexus of rats was investigated. The 5-HT 1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus was also investigated. It was observed that chronic ethanol treatment significantly increased the 5-HT-stimulated [ 3H]inositol 1-phosphate ([ 3H]IP 1) formation, as well as the density ( B max) of 5-HT 1C receptors without causing a significant change in affinity ( K D) of [ 3H]mesulergine binding in rat choroid plexus. It was also observed that chronic ethanol consumption had no significant effect on the B max or K D of 5-HT 1C receptor binding sites in the hippocampus and cortex brain regions of rats. These results thus suggest that chronic ethanol consumption causes an up-regulation of both 5-HT 1C receptors and 5-HT 1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus but has no significant effects on the 5-HT 1C receptors in brain. These results also suggest that 5-HT 1C receptors and their functional response may be involved in the pathogenesis of alcohol dependence.