Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4-methylenedioxymethamphetamine.
Brain Research May 1, 1992 DOI: 10.1016/0006-8993(92)90713-j (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study (in vivo microdialysis in rats) Peer reviewed |
|---|---|
| Population | Awake, freely moving rats (Wistar) |
| Interventions | Methamphetamine 3 4-Methylenedioxymethamphetamine (MDMA) |
| Dose | Methamphetamine 7.5 mg/kg i.p. every 2 h for 3 injections; MDMA 9.2 and 13.8 mg/kg |
| Duration | Repeated dosing over 4 hours (3 injections every 2 h); striatal tissue measured 7 days after administration |
| Topics | MDMA |
| Keywords | Corpus striatum Animals Rats, wistar Dopamine Methamphetamine N-methyl-3,4-methylenedioxyamphetamine 3,4-dihydroxyphenylacetic acid Taurine Aspartic acid Glutamates Neurotoxins Designer drugs Dialysis Analysis of variance Kinetics Time factors Reference values Male |
| Key findings | Repeated methamphetamine increased striatal glutamate efflux and, seven days later, reduced striatal dopamine, whereas MDMA did not raise glutamate but at 13.8 mg/kg reduced striatal serotonin. The authors suggest methamphetamine's long-term dopamine neurotoxicity is mediated in part by a delayed increase in extracellular glutamate, while MDMA's serotonin depletion is not accompanied by glutamate changes. |
Abstract
The effect of repeated administration of either methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA) or vehicle on the extracellular concentrations of glutamate (GLU), aspartate, taurine, dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was studied in awake, freely moving rats using in vivo microdialysis. MA (7.5 mg/kg, i.p.) administered every 2 h for a total of 3 injections, increased the extracellular concentration of GLU in the anteromedial striatum. By contrast, neither vehicle nor MDMA (9.2 and 13.8 mg/kg) increased GLU efflux following repeated administration. Both MA and MDMA increased the extracellular concentration of DA in the striatum. However, the cumulative increase in DA was significantly greater in the MDMA treated animals as compared to the MA group. The concentrations of DA, serotonin (5-HT) and their metabolites were determined in the striatum 7 days following the repeated administration of MA, MDMA and vehicle. MA, but not MDMA or vehicle, decreased the concentration of DA in the striatum. Conversely, MDMA (13.8 mg/kg) decreased the concentration of 5-HT, whereas MA, MDMA (9.2 mg/kg) and vehicle had no effect on striatal 5-HT content. These data are suggestive that the long-term (7 day) DA neurotoxicity produced by the repeated administration of MA is mediated, in part, by a delayed increase in extracellular concentrations of GLU. In contrast, repeated administration of MDMA, at a dose which produced a long-term (7 day) depletion of striatal 5-HT content, had no effect on GLU efflux in the striatum.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine Life Science July 24, 2013
- MDMA (‘ecstasy’) enhances basal acetylcholine release in brain slices of the rat striatum European Journal of Neuroscience April 1, 2000
- Persistent cerebrovascular effects of MDMA and acute responses to the drug European Journal of Neuroscience July 1, 2006
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Cites 9
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
- Microdialysis studies on 3,4-methylenedioxyamphetamine and structurally related analogues. European Journal of Pharmacology July 23, 1991
- Effect of 3,4‐Methylenedioxymethamphetamine on 3,4‐Dihydroxyphenylalanine Accumulation in the Striatum and Nucleus Accumbens Journal of Neurochemistry March 1, 1990
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