Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, mediates rapid inhibition via GABAA receptors (GABAA-R). These are ligand-gated chloride ion channels that were first identified pharmacologically as being activated by GABA and the selective agonist muscimol, blocked by bicuculline and picrotoxin, and modulated by benzodiazepines, barbiturates, and certain other CNS depressants (Macdonald & Olsen, 1994; Sieghart, 1995). GABAA-R mediate rapid phasic inhibitory synaptic transmission, and also tonic inhibition by producing currents in extrasynaptic and perisynaptic locations (Mody & Pearce, 2004; Farrant & Nusser, 2005). Due to their widespread localization throughout the mammalian nervous system, GABAA-R play a major role in virtually all brain physiological functions and serve as targets of numerous classes of drugs, both used clinically and important as research tools (Hevers & Lüddens, 1998; Olsen & Martin, 2000).
