Repeated Administration of 3,4-Methylenedioxymethamphetamine (MDMA) Elevates the Levels of Neuronal Nitric Oxide Synthase in the Nigrostriatal System: Possible Relevance to Neurotoxicity.
Giulia Costa, Micaela Morelli, Nicola Simola
Neurotoxicity Research November 2018 DOI: 10.1007/s12640-018-9892-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Mice treated with MDMA and sacrificed at various times after treatment discontinuation |
| Intervention | MDMA |
| Dose | 10 mg/kg i.p., twice a day/twice a week |
| Duration | 14, 28, or 36 administrations; sacrificed at different time-points after treatment discontinuation, including 3 days and 3 months |
| Measures | immunohistochemistry for nNOS-positive neurons |
| Topics | MDMA |
| Keywords | Amphetamine-related drugs Caudate-putamen Neurotoxicity |
| Key findings | MDMA increased nNOS-positive neurons in the caudate-putamen after 28 or 36 administrations, persisting up to 3 months after treatment ended, and in the substantia nigra pars compacta only after 28 administrations measured 3 days after discontinuation. The authors argue these results support the hypothesis that nitric oxide cascade activation participates in MDMA-induced dopaminergic nigrostriatal toxicity, with more marked effects at striatal terminals than nigral neurons. |
Abstract
Previous studies have consistently demonstrated that the amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) induces dopaminergic damage in the mouse brain, and that this effect is most marked in the nigrostriatal system. Moreover, it has been suggested that the overproduction of nitric oxide (NO) may participate in the dopaminergic damage induced by MDMA. To further elucidate this issue, we evaluated the levels of the enzyme nitric oxide synthase (nNOS), which catalyzes the production of NO, in mice treated with regimens of MDMA that induce progressive and persistent neurotoxicity in the dopaminergic nigrostriatal system. Mice received 14, 28, or 36 administrations of MDMA (10 mg/kg i.p.), twice a day/twice a week, and were sacrificed at different time-points after treatment discontinuation. Thereafter, the number of nNOS-positive neurons was quantified by immunohistochemistry in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc). MDMA elevated the numbers of nNOS-positive neurons in the CPu of mice that received 28 or 36 drug administrations. This effect was still detectable at 3 months after treatment discontinuation. Moreover, MDMA elevated the numbers of nNOS-positive neurons in the SNc. However, this effect occurred only in mice that received 28 drug administrations and were sacrificed 3 days after treatment discontinuation. These results are in line with the hypothesis that activation of the NO cascade participates in the toxic effects induced by MDMA in the dopaminergic nigrostriatal system. Moreover, they suggest that activation of the NO cascade induces toxic effects that are more marked in striatal terminals, compared with nigral neurons.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 4
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies. Neural Regeneration Research May 1, 2020
- MDMA and the Brain: A Short Review on the Role of Neurotransmitters in Neurotoxicity. Basic and clinical neuroscience 2020
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
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