Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain.
Deborah L. Commins, Georgetta Vosmer, R. Virus, William L. Woolverton, Charles R. Schuster, Lewis S. Seiden
Journal of Pharmacology and Experimental Therapeutics April 1, 1987 DOI: 10.1016/s0022-5347(25)00317-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats and guinea pigs |
| Intervention | MDMA |
| Dose | 10, 20 or 40 mg/kg twice a day for 4 days (rats); 20 mg/kg (guinea pigs); single 40 mg/kg injection (rats); 80 mg/kg twice a day for 2 days (rats) |
| Duration | 4 days of twice-daily dosing, with assessment 2 weeks after administration; single-dose experiments assessed 2 and 8 weeks after administration; 80 mg/kg regimen given for 2 days |
| Measures | Norepinephrine, dopamine and serotonin (5-HT) levels; Vmax and Km of 5-HT uptake; Fink-Heimer stain |
| Topics | MDMA |
| Key findings | MDMA produced dose-dependent, long-lasting serotonin depletion across multiple brain regions in rats and guinea pigs, with the highest doses also reducing norepinephrine and/or dopamine in some areas. Reduced Vmax of serotonin uptake and Fink-Heimer staining of degenerating axon terminals and cell bodies suggest MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons, with some non-transmitter-containing neocortical neurons also affected. |
Abstract
(+/-)-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.