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-hydroxytryptamine( 2) (5-HT2) antagonist amperozide attenuates the volitional intake of b oth alcohol and cocaine solutions in a free-choice situation. However, another 5-HT2 antagonist, ritanserin, has not been found to reduce al cohol drinking consistently in the rat. In this study, trazodone was c ompared 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 m g/kg or 2.5 mg/kg for three days. Whereas the higher dose of amperozid e 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 wh ether the antagonism of 5-HT2 receptors by amperozide is critical to i ts attenuating effect on preference for alcohol solutions.