Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 241; no. 1; p. 338
• Main Authors: Commins, D L, Vosmer, G, Virus, R M, Woolverton, W L, Schuster, C R, Seiden, L S
• Format: Journal Article
• Language: English
• Published: United States 01-04-1987
• Subjects: 3,4-Methylenedioxyamphetamine - analogs & derivatives; 3,4-Methylenedioxyamphetamine - toxicity; Amphetamines - toxicity; Animals; Brain - cytology; Brain - drug effects; Corpus Striatum - drug effects; Dopamine - metabolism; Kinetics; Male; N-Methyl-3,4-methylenedioxyamphetamine; Neurons - drug effects; Norepinephrine - metabolism; Rats; Rats, Inbred Strains; Serotonin - metabolism; Somatosensory Cortex - drug effects; Synaptosomes - drug effects; Synaptosomes - metabolism; Tissue Distribution
• ISSN: 0022-3565

(+/-)-3,4-Methylenedioxymethylamphetamine (MDMA) was administered s.c. to rats (10, 20 or 40 mg/kg b. wt.) and guinea pigs (20 mg/kg) twice a day for 4 days, 2 weeks before decapitation. Norepinephrine, dopamine and serotonin (5-HT) levels were assayed in the hippocampus, hypothalamus, striatum and neocortex. In rats, MDMA produced dose-dependent reductions in 5-HT in all brain regions examined. The highest dose also reduced norepinephrine and/or dopamine in some regions. The 20-mg/kg dose of MDMA depleted 5-HT in all regions of the guinea pig brain assayed. In both species, repeated administration of 20 mg/kg of MDMA reduced the Vmax but not the Km of 5-HT uptake 2 weeks after administration. A single 40-mg/kg injection of MDMA depleted 5-HT 2 and 8 weeks after administration to rats in all regions of the brain examined except the hypothalamus. Administration of 80 mg/kg of MDMA twice a day for 2 days to rats depleted striatal 5-HT and dopamine. Brain sections from rats injected with MDMA according to this dosage regimen were stained by the Fink-Heimer method. Degenerating axon terminals and cell bodies were observed in the striatum and somatosensory cortex, respectively. These findings suggest that MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons. Some neurons that do not contain these transmitters (neocortical neurons) are also affected.