Inhibitory effect of dehydroepiandrosterone on brain monoamine oxidase activity: In vivo and in vitro studies

AimsTo evaluate the acute effect of dehydroepiandrosterone (DHEA) on monoamine oxidase (MAO) activity in the corpus striatum (CS) and the nucleus accumbens (NAc) in vivo and in vitro.Main methodsMale Wistar rats received an i.p. injection of DHEA (30, 60 and 120 mg/kg) and MAO activity was assayed by formation of 4-hydroxyquinoline 2 h later. For in vitro studies, DHEA (100 nM–1 mM) was added to brain tissue homogenates to assay MAO activity.Key findingsDHEA significantly reduced (− 24%) total MAO activity in the NAc (F = 8.5, p < 0.001), but not in the CS, at 120 mg/kg dose. No significant difference was observed when MAO A and MAO B activities were independently analyzed. When assayed in vitro, total MAO, MAO A and MAO B activities were reduced by DHEA to 55.7, 28.2 and 54.4% in the NAc and to 71.9, 44.2 and 61.2% in the CS, respectively (IC50 4.7–56.1 µM).SignificanceAn inhibitory effect of DHEA on MAO activity may be involved in the antidepressant and neuroprotective effects of the steroid. Since MAO inhibition reduces neurodegeneration in clinical trials for Parkinson's disease, our results suggest that DHEA may be useful to treat depression and to prevent neuronal death in this disorder.