The acute and chronic effects of MDMA (Ecstasy) on cortical 5-HT2A receptors in rat and human brain

While the pre-synaptic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons have been studied extensively, little is known about its effects on post-synaptic 5-HT2 receptors. Therefore, cortical 5-HT2A receptor densities and 5-HT concentration were studied in MDMA treated rats (10 mg/kg s.c.). Furthermore, 5-HT2A post-synaptic receptor densities in the cerebral cortex of recent as well as ex-MDMA users were studied using [I-123]R91150 SPECT. In rats we observed a decrease followed by a time-dependent recovery of cortical 5-HT2A receptor densities, which was strongly and positively associated with the degree, of 5-HT depletion. In recent MDMA users, post-synaptic 5-HT2A receptor densities, were significantly lower in! all cortical areas studied, while 5-HT2A receptor densities were significantly higher in the occipital cortex of ex-MDMA users. The combined results of this study suggest a compensatory upregulation of post-synaptic 5-HT2A receptors in the occipital cortex of ex-MDMA users due to low synaptic 5-HT levels. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.