Extrasynaptic GABAA receptors in the crosshairs of hormones and ethanol

Gamma-aminobutyric acid (GABA) is the main chemical inhibitory neurotransmitter in the brain. In the central nervous system (CNS) it acts on two distinct types of receptor: an ion channel, i.e., an "ionotropic" receptor permeable to Cl- and HCO3- (GABA(A) receptors) and a G-protein coupled "metabotropic" receptor that is linked to various effector mechanisms (GABA(B) receptors). This review will summarize novel developments in the physiology and pharmacology of GABA(A) receptors (GABA(A)Rs), specifically those found outside synapses. The focus will be on a particular combination of GABA(A)R subunits sensitive to ovarian and adrenal cortical steroid hormone metabolites that are synthesized in the brain (neurosteroids) and to sobriety impairing concentrations of ethanol. These receptors may be the final common pathway for interactions between ethanol and ovarian and stress-related neurosteroids. (C) 2007 Elsevier Ltd. All rights reserved.