Effects of repeated doses of aspartame on serotonin and its metabolite in various regions of the mouse brain.

Following a finding that single doses (approximating to average intakes and to potential 'over-use') of aspartame administered orally to mice caused significant increases in norepinephrine and dopamine concentrations in various brain regions, the effect of repeated exposure to aspartame was studied. Male CD-1 mice were given a daily oral dose of 0, 13, 133 or 650 mg/kg for 30 days and 1 day after the last dose the animals were decapitated and their brain regions were quickly isolated. Analyses of the different regions for catecholamine and indoleamine neurotransmitters and their major metabolites indicated that the increases in adrenergic chemicals observed shortly after a single exposure were not apparent after repeated dosing. In contrast, concentrations of serotonin and its metabolite, 5-hydroxyindoleacetic acid, were decreased in several regions. An increased supply of phenylalanine may be responsible for a decrease in tryptophan uptake by the brain tissue or for a depression in tryptophan conversion to serotonin.