In vivo detection of short‐ and long‐term MDMA neurotoxicity—a positron emission tomography study in the living baboon brain

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](+)McN 5652 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. Synapse 29:183–192, 1998. © 1998 Wiley‐Liss, Inc.