AMPEROZIDE, A 5-HT(2) ANTAGONIST, ATTENUATES CRAVING FOR COCAINE BY RATS

Amperozide, a novel 5-HT2 receptor antagonist with little affinity for the dopamine receptor, suppresses the intake of alcohol in rats witho ut affecting food intake or inducing other side effects. Because of th ese actions, amperozide was examined for its efficacy on the oral pref erence 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 cocai ne per day in a two-choice paradigm. A solution of 0.02% to 0.06% coca ine plus 0.03% saccharin in water was offered to each animal simultane ously with a solution of only 0.03% saccharin in water. The consumptio n 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 injecti ons of amperozide but also during the 4-day posttreatment period. Ampe rozide exerted little or no effect on the intake of food or on body we ight. Radioligand binding experiments confirmed that amperozide has at least a twentyfold greater affinity for 5-HT2 receptors in the fronta l cortex of the rat, as compared to striatal DA1 and DA2 receptors, wi th the proportion value similar to that of the 5-HT2 receptor antagoni st, ritanserin. It is concluded, therefore, that amperozide, which pro duces little or no adverse side effects, appears to be potentially use ful for the treatment of the addiction to cocaine.