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-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.
Reneman
Liesbeth
L
Graduate School of Neurosciences, Department of Nuclear Medicine Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. l.reneman@amc.uva.nl
Endert
Erik
E
de Bruin
Kora
K
Lavalaye
Jules
J
Feenstra
Mathijs G
MG
de Wolff
Freek A
FA
Booij
Jan
J
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000008:administration & dosage*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D010880:Piperidines; C105020:R 91150; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine