Specific inhibition of α5 subunit-containing gabaa receptors enhances loco-motor activity and neuronal activity in the motor cortex

Abstract

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervousystem (CNS). This study examined the effect of specific inhibition of α5 subunit-containinGABAA receptors (α5GABAAR) on the behavioral profile and neuronal activity of the CNS usina compound called L-655,708, which is a selective negative allosteric modulator of α5GABAARL-655,708 administration significantly increased locomotor activity without anxiety-related behav-ior. Furthermore, L-655,708 administration significantly increased c-Fos mRNA expression (a neuronal activity marker) in motor area of the cerebral cortex, whereas it hardly altered c-Fos mRNexpression in the sensory cortex, hippocampus, and spinal cord. This study revealed for the firstime that alteration of neuronal activity with specific inhibition of α5GABAAR differs dependinon each CNS region. α5GABAA R could be a potential target for modulating CNS excitability anbehavioral activity.