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Fornai F, Giorgi FS, Gesi M, Chen K, Alessandri MG, Shih JC.
“Biochemical Effects of the Monoamine Neurotoxins DSP-4 and MDMA in Specific Brain Regions of MAO-B-Deficient Mice”.
synapse. 2001;39:213-21.
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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 32, 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.
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