In vivo administration of valproate reduces the nerve terminal (synaptosomal) activity of GABA aminotransferase in discrete brain areas of rats

Abstract

Previous in vitro experiments have indicated that neuronal GABA aminotransferase (GABA-T) differs from extraneuronal GABA-T in sensitivity to certain enzyme inhibitors, including the antiepileptic drug valproate (VPA). In the present experiments, it was studied if GABA-T activity in whole tissue and synaptosomes prepared from whole tissue of 11 brain regions of rats is affected in vivo by treatment with an anticonvulsant dosage of VPA. For this purpose, rats were treated with VPA, 200 mg/kg i.p., 15 min prior to dissection of brain regions. Synaptosomes were prepared from the 11 brain regions by a density gradient centrifugation method. In whole tissue samples of brain regions, no alteration of GABA-T activity was determined after VPA administration, except a small decrease in the tectum. In contrast, VPA significantly decreased GABA-T activity in synaptosomal fractions of substantia nigra, pons and medulla oblongata. These data substantiate that synaptosomal GABA-T is more susceptible to the inhibitory effect of VPA than the extra-synaptosomal enzyme. Furthermore, since VPA seems to be homogeneously distributed across brain regions, the observation of regional differences in inhibitory effects on GABA-T might indicate differences in the biochemical properties of GABA-T from different brain regions.