The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain.
D M Stone, D C Stahl, Glen R. Hanson, James W. Gibb
European Journal of Pharmacology August 22, 1986 DOI: 10.1016/0014-2999(86)90555-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rat brain tissue (serotonergic and dopaminergic nerve terminal regions) |
| Interventions | MDA MDMA Methamphetamine |
| Dose | 10 mg/kg |
| Topics | MDMA |
| Key findings | Single or repeated 10 mg/kg doses of MDA or MDMA in rats markedly reduced tryptophan hydroxylase activity and serotonin and 5-HIAA levels in serotonergic terminal regions, resembling p-chloroamphetamine. Unlike repeated methamphetamine, repeated MDA or MDMA did not reduce striatal dopamine or tyrosine hydroxylase activity; a single dose raised striatal dopamine, but repeated dosing returned dopamine to control levels while homovanillic acid remained elevated, suggesting effects on dopamine turnover. |
Abstract
The effects of two amphetamine-like designer drugs, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), on dopaminergic and serotonergic systems in the rat brain were investigated and compared to those of methamphetamine (METH). Like METH, single or multiple 10 mg/kg doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in several serotonergic nerve terminal regions. In all regions examined, the reduction in 5-HT content corresponded to the depression of TPH activity. Unlike multiple METH administrations, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. At this time, striatal levels of homovanillic acid were significantly elevated suggesting that both drugs influence dopamine turnover. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 132
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 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
- 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
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
and 127 more in the library
Cites 3
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
- Methylenedioxyamphetamine. Clinical description of overdose, death, and review of pharmacology Archives of Internal Medicine October 1, 1981