Ecstasy-induced reduction of the availability of the brain serotonin transporter as revealed by [11C](+)McN5652-PET and the multi-linear reference tissue model: loss of transporters or artifact of tracer kinetic modelling?
| Autor: | Florian Wilke, Winfried Brenner, Malte Clausen, Janos Mester, Kay Uwe Petersen, Ralph Buchert, Lothar Spies, Rainer Thomasius, Frank Thiele |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Statistical noise N-Methyl-3 4-methylenedioxyamphetamine Ecstasy Down-Regulation computer.software_genre Statistical parametric mapping Models Biological chemistry.chemical_compound Voxel Image Processing Computer-Assisted medicine Humans Tissue Distribution Pharmacology (medical) Carbon Radioisotopes Serotonin transporter Serotonin Plasma Membrane Transport Proteins Pharmacology Models Statistical biology medicine.diagnostic_test Brain Reproducibility of Results Binding potential Isoquinolines Psychiatry and Mental health chemistry Positron emission tomography Data Interpretation Statistical Positron-Emission Tomography Hallucinogens biology.protein Female Radiopharmaceuticals Artifacts Psychology McN5652 computer Neuroscience Protein Binding |
| Zdroj: | Journal of Psychopharmacology. 21:628-634 |
| ISSN: | 1461-7285 0269-8811 |
| Popis: | In a previous positron emission tomography (PET) study with the serotonin transporter (SERT) ligand [11C](+)McN5652, we found protracted reduction of the availability of the brain SERT in users of the drug ecstasy. However, the multi-linear reference tissue method for the quantification of SERT availability used in this study is prone to effects of altered levels of statistical noise that c`ould simulate reduction of SERT. The aim of the present study was to take into account this confound by re-evaluation of the data now using a modelling approach that is rather insensitive to alterations in the level of statistical noise. A total of 116 subjects (30 current, 29 former ecstasy users, 29 drug-naive, 28 polydrug controls) in whom [ 11C](+)McN5652-PET had been performed previously were re-evaluated. The equilibrium specific-to-non-specific partition coefficient V" 3 was obtained voxel-wise by application of the simplified reference tissue method (SRTM), which provides quite unbiased results up to rather large noise levels. Voxel-based comparisons between the groups were performed using statistical parametric mapping. V"3 was reduced in the striatum and in the thalamus in current ecstasy users. This was confirmed by volume-of-interest-based analysis. This result suggests that the ecstasy-induced reduction of SERT availability in SERT-rich brain regions reported previously indicates reduced SERT binding potential rather than being an artifact of tracer kinetic modelling. SRTM analysis did not confirm previous findings in neocortical brain areas. |
| Databáze: | OpenAIRE |
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