Inhibition of a tonic inhibitory conductance in mouse hippocampal neurones by negative allosteric modulators of alpha 5 subunit-containing gamma-aminobutyric acid type A receptors: implications for treating cognitive deficits

摘要

Background: Multiple cognitive and psychiatric disorders are associated with an increased tonic inhibitory conductance that is generated by alpha 5 subunit-containing gamma-aminobutyric acid type A (alpha 5 GABA(A)) receptors. Negative allosteric modulators that inhibit alpha 5 GABA(A) receptors (alpha 5-NAMs) are being developed as treatments for these disorders. The effects of alpha 5-NAMs have been studied on recombinant GABA(A) receptors expressed in non-neuronal cells; however, no study has compared drug effects on the tonic conductance generated by native GABA(A) receptors in neurones, which was the goal of this study.