The effects of the 5-HT1a/5-HT7 agonist 8-OHDPAT were compared across suprachiasmatic (SCN) slices taken from rats given a neurotoxic regimen (1 daily dose for 3 consecutive days, with doses ascending from 10 mg/kg to 20 mg/kg) of MDMA, fenfluramine, or saline 1 week or 20 weeks prior to sacrifice. When applied alone, 8-OHDPAT produced a phase advance observed in slices. Both MDMA and fenfluramine given either 1 or 20 weeks prior to sacrifice dampened the phase advance produced by 8-OHDPAT. A longer interval between drug administration and study (20 wks versus 1 wk) produced less attenuation of 8-OHDPAT-induced phase advance. It appears that neither MDMA nor fenfluramine significantly altered the effects of neuropeptide Y (NPY) or PACAP on suprachiasmatic slices. This in vitro study suggests that repeated administration of MDMA or fenfluramine can affect the mammalian circadian clock. The authors suggest that some of the effects of chronic MDMA use in humans (such as changes in mood or memory) could be due in part to MDMA-induced changes in circadian rhythm.