THE SELECTIVE 5-HT(3) RECEPTOR ANTAGONIST, ONDANSETRON, AUGMENTS THE ANORECTIC EFFECT OF D-AMPHETAMINE IN NONDEPRIVED RATS

Previous behavioural studies have shown that 5-hydroxytryptamine3 (5-H T3) receptor antagonists either block or have no effect on amphetamine -induced effects. The present experiments investigated whether or not the highly selective 5-HT3 receptor antagonist ondansetron would affec t the anorectic effect of a small dose (1 mg/kg) of d-amphetamine. Non deprived male rats were tested in two feeding paradigms: consumption o f a palatable sweetened mash and ingestion of a 3% sucrose solution. O ndansetron (10-100 mug/kg) did not antagonize amphetamine-induced anor exia; instead, in both paradigms consumption was reduced still further when the 5-HT3 antagonist was given in conjunction with amphetamine. Ondansetron given alone had significant effects on consumption, but th e direction of the effect differed according to the paradigm. Sweetene d mash intake was significantly increased at 30 and 100 mug/kg, while sucrose ingestion was significantly reduced at 10 and 30 mug/kg ondans etron. ft is suggested that ondansetron has two opposing effects on in take, one of which (hyperphagia) can be masked by d-amphetamine, leavi ng an anorectic effect that augments that of d-amphetamine.