Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol

Both 5-HT1A and 5-HT2A receptors have been implicated in modulating ethanol self-administration. A novel serotonergic compound, FG 5974, with combined 5-HT1A agonist/5-HT2A antagonist activities, has shown effects in decreasing ethanol consumption in two-bottle choice paradigms. In the present study, the effect of this compound on operant responding for ethanol (as well as water and a saccharin solution) was compared to compounds possessing the separate neuropharmacological effects of this drug (the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT2A antagonist, amperozide). While all three serotonergic compounds decreased operant responding for ethanol, only FG 5974 had no effect on water and saccharin responding. These results suggest that combined 5HT1A agonist/5-HT2A antagonist activity provides a more selective effect on ethanol reinforcement than either neuropharmacological action alone. Therefore, further analysis of mixed serotonergic compounds in general, and FG 5974 in particular, is warranted as they offer potential treatments for alcoholism.