The roles played by serotonin, dopamine and activation of several serotonin receptors in producing acute changes in locomotor activity and responding for conditioned reinforcement after MDMA administration was examined in rats injected with saline, 1.25, 2.5 or 5 mg/kg MDMA. Locomotor activity was measured via activity chamber and photobeam interruption, and response for conditioned reinforcers was measured via a two-lever procedure. Rats in the conditioned reinforcer studies were water-restricted, and lights and tone preceding the delivery of water served as the CR. Rats in receptor site studies were given combinations of 2.5 mg/kg MDMA and one of the following; the 5-HT1B/D antagonist GR127935, the 5HT2A antagonist ketanserin or the 5HT2C antagonist SB242084. All pre-treatments were administered 30 min before MDMA. MDMA dose-dependently increased locomotion, with activity increasing incrementally after each dose, starting at the lowest dose (1.25 mg/kg). Locomotion after MDMA was attenuated by the 5HT1B/D antagonist and by the 5HT2A antagonist. Neither of these 5HT receptor antagonists reduced locomotion when given alone. However, the 5HT2C antagonist enhanced degree of locomotion after MDMA. Two groups of rats, one given MDMA alone and one MDMA + 5HT2C antagonist were sacrificed and brain MDMA was measured via EC-GS; no differences in brain MDMA concentrations were found between the two conditions. MDMA attenuated responding for CR, though response on the CR lever was always higher than the non-CR lever. General responding on either lever was reduced at 5 mg/kg MDMA (highest dose used). Neither the 5HT1B/D antagonist nor the 5HT2A antagonist altered reduced response for conditioned reinforcers after MDMA. Pretreatment with the 5HT2C antagonist increased responding for the CR lever after MDMA. Taken together, the study findings suggest that increased locomotion after MDMA is inhibited by 5HT2C activation, and that attenuated responding for conditioned reinforcers is also reduced through 5HT2C activation. Interactions between serotonin and dopamine are proposed as causes of this behavioral profile, and the changes in locomotion are proposed to arise as a result of indirect, rather than direct, dopamine (DA) release. It is possible but not certain that humans might also be less attentive or responsive to cues relating to hunger or thirst after MDMA. However, it is unclear whether responses seen in rat studies have any relevance to water or food-consumption behavior reported in humans after ecstasy use.