α2-containing GABA_A receptors: A target for the development of novel treatment strategies for CNS disorders

GABA_A receptors have important physiological functions, as revealed by pharmacological studies and experiments involving gene-targeted mouse models, and are the target of widely used drugs such as the benzodiazepines. In this review, we are summarizing current knowledge about the function of α2-containing GABA_A receptors, a receptor subtype representing approximately 15-20% of all GABA_A receptors. This receptor subtype mediates anxiolytic-like, reward-enhancing, and antihyperalgesic actions of diazepam, and has antidepressant-like properties. Secondary insufficiency of α2-containing GABA_A receptors has been postulated to play a role in the pathogenesis of schizophrenia, and may be involved in cognitive impairment in other disorders. Moreover, polymorphisms in the GABRA2 gene encoding the GABA_A receptor α2 subunit have been found to be linked to chronic alcohol dependence and to polydrug abuse. Thus, α2-containing GABA_A receptors are involved in the regulation and/or modulation of emotional behaviors and of chronic pain, and appear to be a valid target for novel therapeutic approaches for the treatment of anxiety, depression, schizophrenia and chronic pain.