Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice

Previous studies reported that drugs acting as monoamine oxidase (MAO)-B in hibitors prevented biochemical effects induced by the neurotoxins N-(2-chlo roethyl)-N-ethyl-2-bromobenzylamine (DSP-4) and 3,4-methylenedioxymethamphe tamine (MDMA, "ecstasy"). In this study, we administered DSP-4 (50 mg/kg) o r MDMA (50 mg/kg X2, 2 h apart) to MAO-B deficient mice. Monoamine content in various brain regions (cerebellum, frontal cortex, hippocampus, hypothal amus, striatum, substantia nigra) was assayed 1 week after neurotoxin admin istration. Injection of DSP-4 to wild-type mice caused a marked norepinephr ine (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 inve stigated. These results suggest that MAO-B is not involved in DSP-4 toxicit y. In wild-types, the neurotoxin MDMA induced both serotonin (5HT) and dopa mine (DA) depletion in specific brain areas. In MAO-B-deficient mice, 5HT d epletion observed in wild-types did not occur. In contrast, MDMA produced a more pronounced DA loss in knockout mice compared with wild-types. The pre sent findings, together with previous data obtained using selective enzyme inhibitors, suggest that MAO-B is not involved in the mechanism of action o f DSP-4, whereas it plays opposite roles in MDMA-induced DA and 5HT depleti ons. (C) 2001 Wiley-Liss, Inc.