Modulation of a GABA-Ergic Inhibitory Circuit in the In Vitro Hippocampus by Etomidate Isomers

Abstract

A pulse-paired stimulation technique was used to examine the in vitro effects of the isomers of etomidate on synaptic transmission between Schaffer collaterals and CA_t pyramidal cells in the guinea pig hippocampus. Etomidate produced a dose-related, stereospecific, reversible increase in paired-pulse inhibition. Replacement of Cl⁻ by isethionate reversed the inhibition induced by (+)-etomidate. Together with earlier biochemical evidence, these results show that in the mammalian CNS (+)-etomidate enhances central inhibition by increasing the effectiveness of γ-aminobutyric acid (GABA) in a chloride-dependent fashion.