Drug-induced changes in GABA content of nerve endings in 11 rat brain regions. Correlation to pharmacological effects

Abstract

For determination of in vivo drug effects on nerve terminal GABA, a procedure was used which allowed the simultaneous measurement of GABA in nerve endings (synaptosomes) from 11 regions of one rat brain. Synaptosomal fractions were prepared by conventional subcellular fractionation procedures and characterized by electron microscopy. Postmortem increases of GABA during removal and dissection of brain tissue, homogenization and fractionation procedures could be sufficiently minimized by rapid processing of the tissue at low temperatures and inclusion of 3-mercaptopropionic acid (1 mM) in the homogenizing medium. In vivo experiments with the GABA-elevating drugs aminooxyacetic acid (30 mg/kg i.p.) and valproic acid (200 mg/kg i.p.) showed that both drugs caused differential effects on synaptosomal GABA levels in different brain regions. A comparison of these biochemical effects with anticonvulsant effects of both drugs in different seizure models supports the concept that GABA synapses in midbrain areas are critically involved in the control of seizure propagation.