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Biochemical effects of the monoamine neurotoxins DSP‐4 and MDMA in specific brain regions of MAO‐B‐deficient mice
Author(s) -
Fornai Francesco,
Giorgi Filippo S.,
Gesi Marco,
Chen Kevin,
Alessrì Maria G.,
Shih Jean C.
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/1098-2396(20010301)39:3<213::aid-syn1002>3.0.co;2-w
Subject(s) - neurotoxin , mdma , dopamine , serotonin , monoamine neurotransmitter , monoamine oxidase , striatum , chemistry , monoamine oxidase a , 5 ht receptor , monoamine oxidase b , pharmacology , hippocampus , endocrinology , medicine , biology , receptor , biochemistry , enzyme
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 ×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. Synapse 39:213–221, 2001. © 2001 Wiley‐Liss, Inc.