Oral administration of 3,4-methylenedioxymethamphetamine (MDMA) produces selective serotonergic depletion in the nonhuman primate.
S F Ali, Glenn D. Newport, Andrew C. Scallet, Zbigniew Binienda, S A Ferguson, J R Bailey, Merle G. Paule, William Slikker
Neurotoxicology and Teratology March 1, 1993 DOI: 10.1016/0892-0362(93)90067-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational dose-response study in nonhuman primates Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Adult female rhesus monkeys |
| Intervention | MDMA |
| Dose | 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days |
| Duration | 4 consecutive days of treatment; neurochemical analyses 1 month after the last dose |
| Measures | HPLC/EC (for 5-HT and 5-HIAA), home cage behavior |
| Topics | Serotonin MDMA |
| Keywords | Brain Animals Macaca mulatta Dopamine N-methyl-3,4-methylenedioxyamphetamine 3,4-dihydroxyphenylacetic acid Homovanillic acid Hydroxyindoleacetic acid Administration, oral Behavior, animal Dose-response relationship, drug Female |
| Key findings | MDMA produced dose-dependent serotonergic depletion in adult female rhesus monkeys: 20.0 mg/kg significantly decreased 5-HT and 5-HIAA in several cortical and midbrain regions, while lower doses (1.25 and 2.5 mg/kg) had little effect except for reduced hippocampal 5-HT at 2.5 mg/kg. Brain stem and hypothalamus were unaffected at any dose, indicating a selective regional dose-response relationship for MDMA-induced neurotoxicity. |
Abstract
MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and home cage behavior as endpoints. Adult female rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors were measured in the home cage prior to, during, and after MDMA treatment. One month after the last dose, the animals were sacrificed and brains dissected into several regions for neurochemical analyses. 5-HT and 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations in any brain region except hippocampus in which 5-HT concentrations were decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decreased 5-HT and 5-HIAA concentrations in several cortical and midbrain structures. However, 5-HT and 5-HIAA concentrations in brain stem and hypothalamus were not significantly altered after any dose of MDMA. Combined with previous data from this laboratory, these results indicate that the decreased concentrations of 5-HT and 5-HIAA in selected brain regions show a selective dose-response relationship for MDMA-induced neurotoxicity as measured by serotonergic depletion in the nonhuman primate.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
- Cerebral1H MRS alterations in recreational 3,4-methylenedioxymethamphetamine (MDMA, ?ecstasy?) users Journal of Magnetic Resonance Imaging October 1, 1999
- Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of frontal dysfunction Journal of Psychopharmacology March 30, 2006
- In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users Archives of General Psychiatry June 6, 2011
- Deconstructing Ecstasy: The Politics Of Mdma Research Addiction Research & Theory 2000
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Cites 6
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- Lasting Neuropsychiatric Sequelae of (??)Methylenedioxymethamphetamine (???Ecstasy???) in Recreational Users Journal of Clinical Psychopharmacology October 1, 1991
- 3,4-Methylenedioxymethamphetamine ("ecstasy") selectively destroys brain serotonin terminals in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics June 1, 1989
- Toxic effects of MDMA on central serotonergic neurons in the primate: importance of route and frequency of drug administration. Brain Research April 12, 1988
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