Serotonin2C receptors and serotonin2C receptor-mediated phosphoinositide hydrolysis in the brain of alcohol-preferring and alcohol-nonpreferring rats.

To examine the role of serotonin2C (5HT2C) receptors in alcohol drinking behavior, the binding indices of 5HT2C receptors were determined in various brain regions of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. 5HT2C receptor-mediated phosphoinositide hydrolysis in the choroid plexus of P and NP rats was also determined. It was observed that the densities of 5HT2C receptors are significantly higher in the hippocampus, the amygdala, and the choroid plexus, but not in the cortex of P rats compared with NP rats. The Kd values of [3H]mesulergine binding to 5HT2C receptors were not different in these brain regions of P rats compared with NP rats. It was also observed that 5HT-stimulated [3H]inositol 1-phosphate formation was significantly higher in the choroid plexus of P rats compared with NP rats. The results of this study indicate that the numbers of 5HT2C receptors are higher in the hippocampus, the amygdala, and the choroid plexus, and that 5HT2C receptor-mediated phosphoinositide hydrolysis is more elevated in the choroid plexus of P rats compared with NP rats. Thus, it seems from these results that increased 5HT2C receptors may be involved in the genetic vulnerability to alcohol drinking behavior.