MDMA-evoked changes in [11C]raclopride and [11C]NMSP binding in living pig brain

Pedro Rosa-Neto, Albert Gjedde, Aage K. Olsen, Svend B. Jensen, Ole L. Munk, Hideaki Watanabe, Paul Cumming

Research output: Contribution to journalArticlepeer-review

Abstract

Positron emission tomography (PET) studies with radiolabeled dopamine D2-like receptor ligands reveal d-amphetamine-evoked increases in the competition from endogenous dopamine. However, the corresponding effects of methylenedioxymethamphetamine (MDMA, "Ecstasy"), which releases catecholamines and also serotonin, are unknown. Using PET, we measured the binding potentials (pBs) of the benzamide [11C]raclopride and the butyrophenone N-[11C]methylspiperone ([11C]NMSP) in brain of living pigs first in a baseline condition and at 45 and 165 min after infusion of (+A)-MDMA-HCl (1 mg/kg, i.V.). Concomitant studies of cerebral blood flow did not reveal significant perfusion changes in the cerebellum reference region or in striatum, supporting the present use of reference tissue methods for the mapping of MDMA-evoked pB changes. Relative to the baseline pB of [ 11C]raclopride for dopamine D2/3 receptors in striatum (pB = 1.5-2.2), MDMA-treatment reduced pB by 35% in the first posttreatment scan and by 22% in the second posttreatment scan, comparable to changes typically evoked by d-amphetamine at a similar dose. In most previous studies, the in vivo binding of butyrophenones has been nearly insensitive to d-amphetamine-evoked dopamine release. However, we found the baseline pB of [11C]NMSP for dopamine D2-like receptors in striatum (pB = 4-5) was decreased by 30% in the first post-MDMA scan and by 50% in the second post-MDMA scan, irrespective of assumptions about the extent of equilibrium binding attained during the 90-min-long PET recordings. Distinct properties of MDMA such as simultaneous release of dopamine and serotonin in brain may account for the present finding of progressive decline in the availability of [ 11C]NMSP binding sites in striatum.

Original languageEnglish (US)
Pages (from-to)222-233
Number of pages12
JournalSynapse
Volume53
Issue number4
DOIs
StatePublished - Sep 15 2004

Keywords

  • Benzamides
  • Brain
  • Butyrophenones
  • Methylenedioxymethamphetamine(MDMA)
  • N-methylspiperone
  • Pig
  • Raclopride

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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