Effect of acute treatment with sodium valproate on catecholamine and serotonin synthesis in mouse cerebral cortex.

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.