NEW BENZAMIDE-DERIVED 5-HT3 RECEPTOR ANTAGONISTS WHICH PREVENT THE EFFECTS OF ETHANOL ON EXTRACELLULAR DOPAMINE, AND FAIL TO REDUCE VOLUNTARY ALCOHOL INTAKE IN RATS

A set of substituted benzamides, characterized by the presence of a bu lky quinolizidine moiety, were subjected to binding assays for 5-HT3 a nd D-2 receptors on membranes obtained from the bovine area postrema ( [H-3]-GR65630) and the rat striatum ([H-3]-spiperone) respectively. Th ese benzamides resulted unsuitable for the recognition of D-2 receptor s, while a few of them, devoid of 5-HT4 receptor activity, had consist ent affinity for central 5-HT3 receptors, inhibiting also potently the ethanol-induced dopamine efflux from the mesolimbic dopamine terminal region. However they failed in attenuating voluntary alcohol consumpt ion in rats, as observed with several other chemically unrelated 5-HT3 antagonists. Thus the 5-HT3-mediated inhibition of alcohol-induced st riatal release of dopamine by substituted benzamides is not a requisit e for affecting ethanol intake.