3,4-Methylenedioxyamphetamine (MDA) self-administration and neurotoxicity.
L E Markert, D C Roberts
Pharmacology, Biochemistry, and Behavior July 1991 DOI: 10.1016/0091-3057(91)90129-p (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal self-administration study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDA |
| Dose | 0.10, 0.05 and 0.025 mg/injection |
| Key points | MDA supported self-administration in rats at all tested doses, but breakpoints on a progressive ratio schedule were relatively low, indicating moderate reinforcing effects. The highest dose (0.10 mg/injection) produced overdoses and deaths. After self-administration, serotonin (5-HT) was significantly depleted in the hippocampus, which the authors interpret as evidence that repeated low-dose MDA self-administration is selectively neurotoxic. |
Abstract
3,4-Methylendioxyamphetamine (MDA), a drug with both stimulant- and hallucinogen-like properties, has been used for both medical and recreational purposes. The present study examined the reinforcing effects of MDA in rats and evaluated the resulting neurotoxicity. Self-administration of various doses (0.10, 0.05 and 0.025 mg/injection) was examined on a Fixed Ratio 1 (FR1) and a Progressive Ratio (PR) schedule. MDA supported self-administration at all doses on the FR1 schedule, but overdoses and deaths occurred at the 0.10 mg/injection dose. The breakpoints established on the PR schedule were relatively low. High performance liquid chromatography analyses of the cortex, hippocampus, striatum and nucleus accumbens subsequent to MDA self-administration revealed significant depletion of 5-HT in the hippocampus. The results suggest that MDA is moderately reinforcing and that self-administration of low doses of MDA over several days is selectively neurotoxic.
Citations in the library
Cited by 4
- Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Pharmacology 2001
- Microdialysis assessment of the impact of (+)3,4‐methylenedioxymethamphetamine, cocaine, and cocaethylene on serotonergic neurons Drug Development Research September 1, 1994
- Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration. Current Topics in Behavioral Neurosciences 2017
- 3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans. Neuroscience and biobehavioral reviews March 1999
Cites 8
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 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. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- Studies of dioxole ring substituted 3,4-methylenedioxyamphetamine (MDA) analogues. Pharmacology, Biochemistry, and Behavior November 1989
- Behavioral effects of (+-) 3,4-methylenedioxyamphetamine (MDA) and (+-) 3,4-methylenedioxymethamphetamine (MDMA) in the pigeon: interactions with noradrenergic and serotonergic systems. Psychopharmacology 1989
and 3 more in the library