Journal
PHARMACOLOGY & THERAPEUTICS
Volume 136, Issue 2, Pages 142-152Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2012.08.006
Keywords
GABA(A) receptor; Benzodiazepines; Anxiety; Depression; Chronic pain; Schizophrenia
Categories
Funding
- National Institutes of Health [GM086448, MH080006, MH085149, DA027571, DA026578, MH094834, MH095905]
- Eleanor and Miles Shore Harvard Medical School Fellowship
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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 alpha 2-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 alpha 2-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 alpha 2 subunit have been found to be linked to chronic alcohol dependence and to polydrug abuse. Thus, alpha 2-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. (C) 2012 Elsevier Inc. All rights reserved.
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