These studies investigated the effects of the 5-hydroxytryptamine (5-HT) releaser, and re-uptake inhibitor, d-fenfluramine, and the non-selective 5-HT receptor antagonist metergoline, on responding for conditioned reward (CR), and on the potentiation of responding for CR following amphetamine injected into the nucleus accumbens. Water deprived rats were trained to associate a compound stimulus with water delivery during a conditioning phase. During a test phase, water was not delivered but the compound stimulus was delivered according to a random ratio 2 schedule following a response on one of two levers; responding on the other lever was not reinforced. Overall, rats responded at a higher rate on the lever delivering the CR. d-Amphetamine (1, 3 and 10 micrograms) injected into the nucleus accumbens dose-dependently enhanced responding on the CR lever. Treatment with d-fenfluramine (0.5 and 1 mg/kg) reduced responding for the CR, and abolished the potentiating effect of d-amphetamine. Responding on the inactive lever was also reduced by 1 mg/kg but not 0.5 mg/kg d-fenfluramine. The reduction of d-amphetamine's effect on responding for CR was prevented by prior treatment with the 5-HT receptor antagonist metergoline (1 mg/kg). Control experiments showed that changes in thirst and motor performance, as well as deficits in learning ability, cannot account for the effects of d-fenfluramine in this paradigm. In a separate experiment, 1 mg/kg metergoline failed to enhance responding for CR, and to augment the response potentiating effect of a low dose (2 micrograms) of d-amphetamine injected into the nucleus accumbens.(ABSTRACT TRUNCATED AT 250 WORDS)