[Show abstract][Hide abstract] ABSTRACT: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In the present study, positron emission tomography with the tracer alpha-[11C]Methyl-L-Tryptophan (11C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional 11C-AMT trapping and characteristics of MDMA use were also examined.MDMA polydrug users exhibited lower normalized 11C-AMT trapping in pre-frontal, orbitofrontal and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized 11C-AMT trapping in MDMA users was also observed, mainly in the brain stem and in frontal and temporal areas. Normalized 11C-AMT trapping in the brain stem and (pre)frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use.Although the possibility of pre-existing 5-HT alterations predisposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms.This article is protected by copyright. All rights reserved.
Journal of Neurochemistry 07/2014; DOI:10.1111/jnc.12826 · 4.24 Impact Factor
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