Amperozide, a novel 5-HT2 receptor antagonist with little affinity for the
dopamine receptor, suppresses the intake of alcohol in rats without affecting food intake or inducing other side effects. Because of these actions,
amperozide was examined for its efficacy on the oral preference by the rat for a
solution of
cocaine. In this study, rats were selected for their voluntary consumption of at least 10 mg/kg of
cocaine per day in a two-choice paradigm. A
solution of 0.02% to 0.06%
cocaine plus 0.03%
saccharin in water was offered to each animal simultaneously with a
solution of only 0.03%
saccharin in water. The consumption of food and both fluids, as well as
body weight, was recorded daily for three successive periods: 4 days of pretreatment baseline; 3 days during
injections of either
amperozide or the saline vehicle
solution; and 4 days postinjections.
Amperozide was administered SC twice daily in a dose of 0.5, 1.0, or 2.5 mg/kg. The volitional intake of
cocaine was significantly reduced not only during the 3-day period of
injections of
amperozide but also during the 4-day posttreatment period.
Amperozide exerted little or no effect on the intake of food or on
body weight. Radioligand binding experiments confirmed that
amperozide has at least a twentyfold greater affinity for 5-HT2 receptors in the frontal cortex of the rat, as compared to striatal DA1 and DA2 receptors, with the proportion value similar to that of the 5-HT2 receptor antagonist,
ritanserin.(ABSTRACT TRUNCATED AT 250 WORDS)