title: α2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders.
abstract: 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.
authors.affiliation: Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, MA 02478, USA.
authors.forename: Elif
authors.initials: E
authors.lastname: Engin
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
mesh_terms: D000437:Alcoholism / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D059350:Chronic Pain / Q000188:drug therapy / Q000209:etiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D003863:Depression / Q000188:drug therapy / Q000209:etiology; D058785:GABA-A Receptor Agonists / Q000627:therapeutic use*; D006801:Humans; D011110:Polymorphism, Genetic; D011724:Pyridazines / Q000627:therapeutic use; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000209:etiology; D014230:Triazoles / Q000627:therapeutic use
chemical_list: C507018:7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo(4,3-b)pyridazine; D058785:GABA-A Receptor Agonists; C484841:GABRA2 protein, human; D011724:Pyridazines; D011963:Receptors, GABA-A; D014230:Triazoles