We examined the effect of sodium valproate (VPA) on monoamine synthesis in the mouse cerebral cortex by measuring the accumulation of L-3,4-dihydroxyphenylalanine and 5-hydroxytryptophan following inhibition of aromatic L-amino acid decarboxylase. Treatment with VPA decreased catecholamine synthesis, in a dose-dependent manner, with maximum inhibition 60 min following treatment. Muscimol, a GABAA receptor agonist, also decreased catecholamine synthesis, although baclofen, a GABAB receptor agonist, did not. Picrotoxin, a GABAA receptor antagonist, inhibited the VPA-induced decrease in catecholamine synthesis. However, serotonin synthesis was not significantly changed by VPA. These results suggest that acute treatment with VPA reduces the synthesis of catecholamines via GABAA receptors.