Relationship between drug-induced changes in seizure thresholds and the GABA content of brain and brain nerve endings

Abstract

The intraperitoneal administration of gabaculine, aminooxyacetic acid (s.c.), gamma-acetylenic GABA, gamma-vinyl GABA, ethanolamine-O-sulphate, sodium valproate and GABA caused significant increases in the GABA content of both the whole brain and brain nerve endings (synaptosomes) in mice, a linear relationship being observed between the two parameters. When the relative effects on GABA concentrations were compared with the potency of the different drugs to elevate the thresholds for electroconvulsions and clonic pentetrazole seizures, only the increase in the pentetrazole seizure threshold was significantly correlated with the elevation of brain and synaptosomal GABA content. The present results indicate that the threshold for pentetrazole seizures is an appropriate test-system to study the relationship between alterations of overall GABA levels in the brain and nerve terminals and anticonvulsant activity of GABA-elevating agents.