Specific GABAA circuits in brain development and therapy

GABAergic interneurons are highly diverse and operate with a corresponding diversity of GABA(A) receptor subtypes in controlling behaviour. In this article, we review the significance of GABA(A) receptor heterogeneity for neural circuit development and central nervous system pharmacology. GABA(A) receptor subtypes were identified as selective targets for behavioural actions of benzodiazepines and of selected intravenous anesthetic agents using point mutations which render a specific receptor subtype insensitive to the action of the respective drugs and also by novel subtype-selective ligands. The pharmacological separation of anxiolysis and sedation guides the development of novel anxiolytics, while inverse agonism at extrasynaptic GABA(A) receptors involved in learning and memory is currently being evaluated as a novel therapeutic principle for symptomatic memory enhancement. (C) 2004 Elsevier Inc. All rights reserved.