In vivo effects of anticonvulsant drugs on nerve terminal (synaptosomal) GABA levels in 11 brain regions of the rat

Abstract

Thein vivo effects of two GABA-elevating drugs with anticonvulsant properties, namely valproic acid (VPA) and aminooxyacetic acid (AOAA), on nerve terminal GABA levels in discrete rat brain regions were studied by means of a newly developed synaptosomal model. The profile of synaptosomal GABA increases obtained with AOAA was quite different from that seen with VPA. Thus, AOAA (30 mg/kg i.p., 2 hours) caused significant increases in olfactory bulb, cortex, hippocampus, thalamus and cerebellum, whereas VPA (200 mg/kg i.p., 0.5 hour) significantly increased GABA also in hypothalamus, substantia nigra and superior and inferior colliculus. In contrast to the regional selectivity of both drugs with respect to synaptosomal GABA levels, AOAA in most regions was more potent than VPA in increasing whole tissue GABA levels determined prior to subcellular fractionation. The data thus demonstrate that comparison of GABA levels in synaptosomal fractions rather than homogenates from discrete brain areas provides a more sensitive index of the action of GABA-elevating drugs administeredin vivo.