Journal
NEUROPSYCHOPHARMACOLOGY
Volume 30, Issue 9, Pages 1741-1750Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1300736
Keywords
MDMA; neurotoxicity; serotonin transporters; drug abuse; PET; neuroimaging
Categories
Funding
- Intramural NIH HHS [Z01 DA000206] Funding Source: Medline
- NCRR NIH HHS [M01RR002719, M01 RR002719-215804, M01 RR002719-190233, M01 RR002719, M01 RR002719-200233] Funding Source: Medline
- NIAAA NIH HHS [R01 AA011653-05, R01 AA011653-02, R01 AA011653, R01 AA011653-04, AA11653, R01 AA011653-01A1, R01 AA011653-03] Funding Source: Medline
- NIA NIH HHS [R01 AG014400-02, R01 AG014400-03] Funding Source: Medline
- NIDA NIH HHS [DA10217, R01 DA010217, R01 DA010217-04, K02 DA000206, R01 DA010217-06, R01 DA010217-05, R01 DA010217-07, R01 DA010217-08] Funding Source: Medline
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(+/-)3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') is a widely used illicit drug that produces toxic effects on brain serotonin axons and axon terminals in animals. The results of clinical studies addressing MDMA's serotonin neurotoxic potential in humans have been inconclusive. In the present study, 23 abstinent MDMA users and 19 non-MDMA controls underwent quantitative positron emission tomography (PET) studies using [C-11]McN5652 and [C-11]DASB, first- and second-generation serotonin transporter (SERT) ligands previously validated in baboons for detecting MDMA-induced brain serotonin neurotoxicity. Global and regional distribution volumes (DVs) and two additional SERT-binding parameters (DVspec and DVR) were compared in the two subject populations using parametric statistical analyses. Data from PET studies revealed excellent correlations between the various binding parameters of [C-11] McN5652 and [C-11]DASB, both in individual brain regions and individual subjects. Global SERT reductions were found in MDMA users with both PET ligands, using all three of the above-mentioned SERT-binding parameters. Preplanned comparisons in 15 regions of interest demonstrated reductions in selected cortical and subcortical structures. Exploratory correlational analyses suggested that SERT measures recover with time, and that loss of the SERT is directly associated with MDMA use intensity. These quantitative PET data, obtained using validated first- and second-generation SERT PET ligands, provide strong evidence of reduced SERT density in some recreational MDMA users.
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