Chronic treatment with a serotonin(2) receptor (5-HT(2)R) agonist modulates the behavioral and cellular response to (+)-3,4-methylenedioxymethamphetamine [(+)-MDMA].

3,4-Methylenedioxymethamphetamine [MDMA; ecstasy] evokes a multifaceted subjective experience in human users which includes stimulation, feelings of well-being, mood elevation, empathy towards others as well as distortions in time, sensation and perception. Aspects of this unique psychopharmacology of MDMA are thought to be related to its potent actions to release serotonin (5-HT) and indirectly stimulate the 5-HT(2A) receptor (5-HT(2A)R). In the present studies, we examined the interrelationship between down-regulation of 5-HT(2A)R expression and the behaviorally stimulatory effects generated by acute administration of (+)-MDMA, the most potent enantiomer of (+/-)-MDMA.