Valproate enhances GABA turnover in the substantia nigra

The effects of the antiepileptic drug, valproate (VPA), on regional turnover of gamma-aminobutyric acid (GABA) in the rat brain were studied by determining the rate of GABA accumulation following complete inhibition of GABA degradation by aminooxyacetic acid (AOAA). VPA was administered at a dose of 200 mg/kg 5, 15 and 30 min prior to injection of AOAA, 100 mg/kg. In most of the 12 regions examined, VPA did not alter the AOAA-induced GABA accumulation. However, significant increases in GABA accumulation were found in corpus striatum and, more marked, in substantia nigra. Since the substantia nigra has been identified as a substrate for the anticonvulsant action of GABAergic drugs, the data may indicate that the effect of VPA on GABA synthesis rate in this region may be involved in its mechanism of anticonvulsant action.