3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites.
G. Battaglia, S. Yeh, E. O'Hearn, M. Molliver, M. Kuhar, E. Souza
Journal of Pharmacology and Experimental Therapeutics September 1, 1987 DOI: 10.1016/s0022-3565(25)39191-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Rat brain |
| Interventions | MDMA MDA |
| Dose | 20 mg/kg s.c., twice daily for 4 days |
| Duration | 4-day treatment, 2-week follow-up |
| Topics | MDMA Serotonin |
| Citations | 459 |
| Key findings | MDMA and MDA cause long-lasting reductions in serotonin metabolite levels and serotonin uptake site density in rat brain, indicating neurotoxic effects on serotonergic neurons. |
Abstract
This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of [3H]paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of [3H]mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: MDMA Opposes
Repeated MDMA (20 mg/kg twice daily for 4 days) produced long-lasting 50-75% reductions in serotonin uptake site density and 30-60% reductions in serotonin metabolite levels, without long-term catecholamine changes.
Synthesized
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 158
- 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 Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
and 153 more in the library