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

Neuropsychopharmacology. 2002 Mar;26(3):387-96. doi: 10.1016/S0893-133X(01)00366-9.


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-HT(2) receptors. Therefore, cortical 5-HT(2A) receptor densities and 5-HT concentration were studied in MDMA treated rats (10 mg/kg s.c.). Furthermore, 5-HT(2A) post-synaptic receptor densities in the cerebral cortex of recent as well as ex-MDMA users were studied using [123I]R91150 SPECT. In rats we observed a decrease followed by a time-dependent recovery of cortical 5-HT(2A) receptor densities, which was strongly and positively associated with the degree of 5-HT depletion. In recent MDMA users, post-synaptic 5-HT(2A) receptor densities were significantly lower in all cortical areas studied, while 5-HT(2A) 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-HT(2A) receptors in the occipital cortex of ex-MDMA users due to low synaptic 5-HT levels.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Animals
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism*
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Female
  • Humans
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • Piperidines / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism
  • Serotonin Agents / administration & dosage*
  • Tomography, Emission-Computed, Single-Photon / methods
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Piperidines
  • R 91150
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin Agents
  • Serotonin
  • N-Methyl-3,4-methylenedioxyamphetamine