Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice
Francesco Fornai, Filippo Sean Giorgi, Marco Gesi, Kai Chen, Maria G. Alessr�, Jean C. Shih
Synapse 2001 DOI: 10.1002/1098-2396(20010301)39:3<213::aid-syn1002>3.0.co;2-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | MAO-B-deficient and wild-type mice |
| Interventions | DSP-4 MDMA |
| Dose | 50 mg/kg DSP-4; 50 mg/kg x 2 MDMA, 2 h apart |
| Duration | 1 week after neurotoxin administration |
| Topics | MDMA Serotonin |
| Keywords | Neurotoxin Dopamine Monoamine neurotransmitter Striatum Monoamine oxidase a 5-HT Receptor Monoamine oxidase b Pharmacology Hippocampus Endocrinology |
| Citations | 54 |
| Key findings | MAO-B deficiency prevents MDMA-induced serotonin depletion but worsens dopamine loss, and does not affect DSP-4 toxicity. |
Abstract
Previous studies reported that drugs acting as monoamine oxidase (MAO)-B inhibitors prevented biochemical effects induced by the neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). In this study, we administered DSP-4 (50 mg/kg) or MDMA (50 mg/kg x 2, 2 h apart) to MAO-B deficient mice. Monoamine content in various brain regions (cerebellum, frontal cortex, hippocampus, hypothalamus, striatum, substantia nigra) was assayed 1 week after neurotoxin administration. Injection of DSP-4 to wild-type mice caused a marked norepinephrine (NE) loss in specific brain regions. Unexpectedly, DSP-4 caused similar effects in MAO-B-deficient and in wild-type mice in all brain regions investigated. These results suggest that MAO-B is not involved in DSP-4 toxicity. In wild-types, the neurotoxin MDMA induced both serotonin (5HT) and dopamine (DA) depletion in specific brain areas. In MAO-B-deficient mice, 5HT depletion observed in wild-types did not occur. In contrast, MDMA produced a more pronounced DA loss in knockout mice compared with wild-types. The present findings, together with previous data obtained using selective enzyme inhibitors, suggest that MAO-B is not involved in the mechanism of action of DSP-4, whereas it plays opposite roles in MDMA-induced DA and 5HT depletions.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 13
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- Persistent MDMA‐induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice Journal of Neurochemistry September 24, 2008
- MDMA and Seizures: A Dangerous Liaison? Annals of the New York Academy of Sciences August 1, 2006
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- MDMA (ecstasy) enhances loud noise-induced morphofunctional alterations in heart and adrenal gland. Microscopy research and technique September 2011
and 8 more in the library
Cites 6
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- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- Superoxide radicals mediate the biochemical effects of methylenedioxymethamphetamine (MDMA): Evidence from using CuZn‐superoxide dismutase transgenic mice Synapse October 1, 1995
- The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term serotonergic deficits. Journal of Pharmacology and Experimental Therapeutics May 1, 1995
- Inhibition of MAO-B protects against MDMA-induced neurotoxicity in the striatum. Psychopharmacology April 1995
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