MDMA produces dose-dependent increases in reward responsivity, a measure of anhedonia, in rats, along with dose-dependent deficits in attention and short-term memory, and increases in prosocial interaction in male but not female rats. The desirable prohedonic effects and undesirable cognitive disruptions do not persist beyond 24 hours. These results characterize MDMA as a promising prohedonic treatment despite short-lived cognitive impairment following acute administration.
Psilocybin and ketamine acutely increased reward responsiveness in rats, and the effect persisted 24 hours after dosing. The increase from psilocybin, but not ketamine, was blocked by a 5-HT2A receptor antagonist. Other psychedelics, DMT and DOI, also acutely increased reward responsiveness but the effect did not last 24 hours. The non-psychedelic 5-HT2A agonist lisuride and the SSRI fluoxetine had no positive effects. These results suggest psychedelics can produce acute and enduring increases in reward responsiveness, partly through the 5-HT2A receptor, though the time course varies and clinical implications require further validation.