Lasting effects of (+-)-3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: neurochemical observations.
George A. Ricaurte, A L Martello, J L Katz, M B Martello
Journal of Pharmacology and Experimental Therapeutics May 1, 1992 DOI: 10.1016/s0022-3565(25)11083-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Squirrel monkeys (nonhuman primates); three controls and 12 MDMA-treated animals |
| Intervention | MDMA |
| Dose | 5 mg/kg twice daily for 4 consecutive days, subcutaneous |
| Duration | 4-day treatment; assessments at 2 weeks, 10 weeks, 8 months, and 18 months after treatment |
| Measures | regional brain serotonin content, 5-hydroxyindoleacetic acid content, [3H] paroxetine-labeled serotonin uptake sites |
| Topics | Serotonin MDMA |
| Keywords | Brain Neurons Cell membrane Animals Saimiri Norepinephrine Dopamine N-methyl-3,4-methylenedioxyamphetamine 3,4-dihydroxyphenylacetic acid Hydroxyindoleacetic acid Piperidines Paroxetine Serotonin antagonists Injections, subcutaneous Female |
| Key findings | MDMA given to squirrel monkeys at 5 mg/kg twice daily for four days caused profound reductions in serotonergic presynaptic markers at two weeks; partial recovery appeared at ten weeks, but by 18 months deficits had returned to two-week severity in most brain regions. The thalamus and hypothalamus were exceptions, showing recovery or increases above control levels, which the authors suggest may reflect reinnervation or hyperinnervation. |
Abstract
The purpose of this study was to assess the duration of (+-)-3,4-methylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons in nonhuman primates. Fifteen squirrel monkeys were used: three served as controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4 consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were examined for regional brain content of serotonin and 5-hydroxyindoleacetic acid, and for the number of [3H] paroxetine-labeled serotonin uptake sites. Two weeks after MDMA treatment, monkeys showed profound reductions in all three serotonergic presynaptic markers. By 10 weeks, there was evidence of partial recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal cortex). However, by 18 months, it was evident that recovery did not continue, as serotonergic deficits returned to the level of severity observed 2 weeks after MDMA treatment. This was the case in all brain regions examined except the thalamus and hypothalamus. In the thalamus, the level of serotonin increased to 63% of control, whereas that of 5-hydroxyindoleacetic acid recovered completely. In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid were 140 and 187% of control, respectively. These results suggest that MDMA produces lasting effects on serotonergic neurons in nonhuman primates, with most brain regions showing evidence of persistent denervation and some showing signs of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The morphological and functional correlates of these enduring neurochemical changes in the MDMA-treated primate remain to be delineated.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 72
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Journal of Neuroscience June 15, 1999
- Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Journal of Neurology, Neurosurgery, and Psychiatry June 1, 2000
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
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