The Acute and Chronic Effects of MDMA ("Ecstasy")
on Cortical 5-HT(2A) Receptors in Rat and Human Brain

by
Reneman L, Endert E, de Bruin K,
Lavalaye J, Feenstra MG, de Wolff FA, Booij J.
Graduate School of Neurosciences,
Department of Nuclear Medicine Academic Medical Center,
1105 AZ, Amsterdam, The Netherlands
Neuropsychopharmacology 2002 Mar;26(3):387-96


ABSTRACT

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.

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