These studies addressed the question of serotonin (5-HT)-dopamine (DA) interactions with regard to reward-related behavior and motor activity in rats. The first experiment evaluated the effect of chronic treatment with fluoxetine (7 mg/kg/day), a serotonin-selective reuptake inhibitor, and buproprion (15 mg/kg/day), a dopamine reuptake inhibitor, on responding for conditioned reinforcement (CR). Chronic fluoxetine, but not buproprion, enhanced CR responding, and also potentiated cocaine-induced increases in CR responding. In the second experiment, animals received intra-accumbens infusions of either 5-HT (0, 1, 5, and 10 microg) or DA (10, 20 microg) prior to the conditioned reinforcement test. Dopamine, but not 5-HT, selectively facilitated CR responding, although 5-HT non-specifically increased responding as well. In the third and fourth experiments, it was demonstrated that intra-accumbens 5-HT causes increased motor activity, which was partially blocked by DA antagonists. The results suggest that chronically increased levels of 5-HT may facilitate reward-related behavior, but most likely via indirect modulatory mechanisms affecting general arousal and motor tone.