Long-term effects of "ecstasy" use on serotonin transporters of the brain investigated by PET.
Alterations of the serotonergic system due to ecstasy consumption have been extensively documented in recent literature. However, reversibility of these neurotoxic effects still remains unclear. To address this question, PET was performed using the serotonin transporter (SERT) ligand (11)C-(+)-McN5652 in a total of 117 subjects subdivided into 4 groups: actual ecstasy users (n = 30), former ecstasy users (n = 29), drug-naive control subjects (n = 29), and subjects with abuse of psychoactive agents other than ecstasy (n = 29).


METHODS
About 500 MBq (11)C-(+)-McN5652 were injected intravenously. Thirty-five scans were acquired according to a dynamic scan protocol of 90 min using a full-ring whole-body PET system. Transaxial slices were reconstructed using an iterative method. Individual brains were transformed to a template defined earlier. Distribution volume ratios (DVRs) were derived by application of a reference tissue approach for reversible binding. Gray matter of the cerebellum served as reference. SERT-rich brain regions--mesencephalon, putamen, caudate, and thalamus--were selected for the evaluation of SERT availability using volumes of interest predefined in the template.


RESULTS
Compared with drug-naive control subjects, the DVR in actual ecstasy users was significantly reduced in the mesencephalon (P = 0.004) and the thalamus (P = 0.044). The DVR in former ecstasy users was very close to the DVR in drug-naive control subjects in all brain regions. The DVR in polydrug users was slightly higher than that in the drug-naive control subjects in all SERT-rich regions (not statistically significant).


CONCLUSIONS
Our findings further support the hypothesis of ecstasy-induced protracted alterations of the SERT. In addition, they might indicate reversibility of the availability of SERT as measured by PET. However, this does not imply full reversibility of the neurotoxic effects.
Buchert
Ralph
R
Department of Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany. buchert@uke.uni-hamburg.de
Thomasius
Rainer
R
Nebeling
Bruno
B
Petersen
Kay
K
Obrocki
Jost
J
Jenicke
Lars
L
Wilke
Florian
F
Wartberg
Lutz
L
Zapletalova
Pavlina
P
Clausen
Malte
M
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006213:Hallucinogens / Q000009:adverse effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007546:Isoquinolines; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D019966:Substance-Related Disorders / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D006213:Hallucinogens; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C058079:McN 5652; D018817:N-Methyl-3,4-methylenedioxyamphetamine