In vivo detection of short- and long-term MDMA neurotoxicity--a positron emission tomography study in the living baboon brain
| Autor: | U, Scheffel, Z, Szabo, W B, Mathews, P A, Finley, R F, Dannals, H T, Ravert, K, Szabo, J, Yuan, G A, Ricaurte |
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| Rok vydání: | 1998 |
| Předmět: |
Brain Chemistry
Male Serotonin Plasma Membrane Transport Proteins Brain Diseases Carbon Isotopes Membrane Glycoproteins N-Methyl-3 4-methylenedioxyamphetamine Brain Membrane Transport Proteins Nerve Tissue Proteins Isoquinolines Iodine Radioisotopes Radioligand Assay Serotonin Agents Cocaine Animals Autoradiography Serotonin Antagonists Carrier Proteins Papio Tomography Emission-Computed |
| Zdroj: | Synapse (New York, N.Y.). 29(2) |
| ISSN: | 0887-4476 |
| Popis: | The present study evaluated short- and long-term effects of MDMA (3,4-methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN 5652, a potent 5-HT transporter ligand, as well as [11C]RTI-55, a cocaine derivative which labels both 5-HT and dopamine transporters. Following baseline PET scans with [11C](+)McN5652, [11C](-)McN5652 (the inactive enantiomer of the active enantiomer [11C](+)McN5652) and [11C]RTI-55, a baboon was treated with MDMA (5 mg/kg, s.c., twice daily for four consecutive days). PET studies at 13, 19, and 40 days post-MDMA revealed decreases in mean radioactivity levels in all brain regions when using [11C](+)McN 5652, but not with [11C](-)McN5652 or [11C]RTI-55. Reductions in specific [11C](+)McN5652 binding (calculated as the difference in radioactivity concentrations between (+) and (-)[11C]McN5652) ranged from 44% in the pons to 89% in the occipital cortex. PET studies at 9 and 13 months showed regional differences in the apparent recovery of 5-HT transporters, with increases in some brain regions (e.g., hypothalamus) and persistent decreases in others (e.g., neocortex). Data obtained from PET studies correlated well with regional 5-HT axonal marker concentrations in the CNS measured after sacrifice of the animal. The results of these studies indicate that PET imaging of the living nonhuman primate brain with [11C](+)McN5652 can detect changes in regional 5-HT transporter density secondary to MDMA-induced neurotoxicity. Using PET, it should also be feasible to use [11C](+)McN5652 to determine whether human MDMA users are also susceptible to MDMA's neurotoxic effects. |
| Databáze: | OpenAIRE |
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