MDMA and learning: effects of acute and neurotoxic exposure in the rat.

In two experiments, the effects of MDMA on the acquisition of lever-press responding of rats were examined under procedures in which water delivery was delayed by 0, 10, or 20 s relative to the response that produced it. In the first study, experimentally naive, water-deprived rats received an intraperitoneal injection of MDMA (0, 1.0, 3.2, or 5.6 mg/kg) prior to one 8-h experimental session. Response acquisition was observed under all conditions at all drug doses. MDMA increased the total number of responses emitted and the total number of water deliveries earned in dose-dependent fashion, but only when reinforcement was immediate. Under conditions of delay, MDMA had no effect on either measure. Under all reinforcement conditions, higher doses of MDMA typically produced an initial reduction in lever pressing, and in that sense interfered with learning. In the second study, rats received an MDMA injection regimen previously shown to be neurotoxic. Control rats received saline solution according to the same injection schedule. Two weeks after completing the regimen, rats were water deprived and exposed to behavioral procedures as described for the first experiment. Although MDMA significantly reduced 5-HT and 5-HIAA levels in the striatum and prefrontal cortex, mean performance of rats exposed to MDMA did not differ from that of rats exposed to vehicle. Twenty-five percent of the rats exposed to MDMA and delayed reinforcement did fail to acquire responding, which suggests that further study of the effects of neurotoxic doses of MDMA on initial response acquisition is warranted.