Comparison of the action of the 5-HT2 antagonists amperozide and trazodone on preference for alcohol in rats.

Previous studies in the rat demonstrated that the 5-hydroxytryptamine2 (5-HT2) antagonist amperozide attenuates the volitional intake of both alcohol and cocaine solutions in a free-choice situation. However, another 5-HT2 antagonist, ritanserin, has not been found to reduce alcohol drinking consistently in the rat. In this study, trazodone was compared to amperozide for its effect on the volitional consumption of alcohol because, like amperozide, trazodone is a potent 5-HT2 receptor antagonist but a weak inhibitor of 5-HT reuptake. Male Sprague-Dawley rats were induced to drink alcohol by 10 mg/kg cyanamide injected for 3 days b.i.d. One week later the rats were offered a choice of water and increasing concentrations of alcohol solutions ranging from 3% to 30% v/v in a three-bottle two-choice paradigm. After the concentration of alcohol that produced maximal daily intake was determined for each rat, trazodone or amperozide was injected b.i.d. SC in doses of 1.0 mg/kg or 2.5 mg/kg for three days. Whereas the higher dose of amperozide produced a significant, 55.6% decrease from pretreatment baseline of alcohol intake, trazodone did not alter alcohol preference at either the 1.0- or 2.5-mg/kg dose. These results are discussed in terms of whether the antagonism of 5-HT2 receptors by amperozide is critical to its attenuating effect on preference for alcohol solutions.