3,4-Methylenedioxymethamphetamine ("ecstasy") selectively destroys brain serotonin terminals in rhesus monkeys.
T. Insel, G. Battaglia, J. Johannessen, S. Marra, E. Souza
Journal of Pharmacology and Experimental Therapeutics June 1, 1989 DOI: 10.1016/s0022-3565(25)23487-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Rhesus monkeys |
| Intervention | MDMA |
| Dose | 2.5 or 10 mg/kg twice daily for 4 days |
| Duration | 4-day treatment; 14-week follow-up in the second study |
| Measures | CSF 5-HIAA, brain serotonin, brain 5-HIAA, serotonin uptake sites |
| Topics | MDMA Serotonin |
| Key findings | Repeated MDMA administration in rhesus monkeys produced selective, persistent reductions in serotonin markers: lowered CSF 5-HIAA and brain serotonin and 5-HIAA, and at high doses decreased serotonin uptake sites in cortex and striatum, suggesting destruction of serotonin terminals, while noradrenergic and dopaminergic measures were generally unaffected. The authors suggest MDMA may produce similar effects in humans. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"), an amphetamine analog, is a "designer drug" which is being increasingly abused. The potential neurotoxic hazard of MDMA in humans was assessed by examining the effects of repeated systemic administration of MDMA on selected neurochemical and behavioral measures in rhesus monkeys. In the first study, MDMA (2.5 or 10 mg/kg twice daily for 4 days) produced selective and significant neurochemical decreases in cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and brain concentrations of serotonin and 5-HIAA. At the high dose of MDMA, a selective decrease in serotonin uptake sites (reflecting destruction of brain serotonin terminals) was observed. To determine if these changes after high dose MDMA were pharmacologic or truly neurotoxic, in a subsequent study monkeys were treated with MDMA (10 mg/kg twice daily for 4 days) and then monitored for 14 weeks. Throughout this period, CSF 5-HIAA was decreased in MDMA-treated animals but not in saline-injected controls. At the end of this period, significant decreases in the concentration of serotonin, 5-HIAA and serotonin uptake sites were observed in cerebral cortex and striatum but not in hypothalamus or spinal cord. In contrast to these widespread alterations in serotonin markers, comparable noradrenergic and dopaminergic measures in CSF and brain appeared generally unaffected. These data demonstrating potent and selective effects of MDMA on various brain serotonin parameters in rhesus monkeys suggest that the drug may produce similar effects in humans.