TY - JOUR
T1 - α2-containing GABAA receptors
T2 - A target for the development of novel treatment strategies for CNS disorders
AU - Engin, Elif
AU - Liu, Jing
AU - Rudolph, Uwe
N1 - Funding Information:
Research by the authors on GABA A receptors was or is supported by grants from the National Institutes of Health to UR (award numbers GM086448 , MH080006 , MH085149 , DA027571 , DA026578 , MH094834 and MH095905 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences, the National Institute of Mental Health and the National Institute of Drug Abuse, or the National Institutes of Health. EE was supported by the Eleanor and Miles Shore Harvard Medical School Fellowship .
PY - 2012/11
Y1 - 2012/11
N2 - GABAA 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 GABAA receptors, a receptor subtype representing approximately 15-20% of all GABAA receptors. This receptor subtype mediates anxiolytic-like, reward-enhancing, and antihyperalgesic actions of diazepam, and has antidepressant-like properties. Secondary insufficiency of α2-containing GABAA 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 GABAA receptor α2 subunit have been found to be linked to chronic alcohol dependence and to polydrug abuse. Thus, α2-containing GABAA 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.
AB - GABAA 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 GABAA receptors, a receptor subtype representing approximately 15-20% of all GABAA receptors. This receptor subtype mediates anxiolytic-like, reward-enhancing, and antihyperalgesic actions of diazepam, and has antidepressant-like properties. Secondary insufficiency of α2-containing GABAA 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 GABAA receptor α2 subunit have been found to be linked to chronic alcohol dependence and to polydrug abuse. Thus, α2-containing GABAA 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.
KW - Anxiety
KW - Benzodiazepines
KW - Chronic pain
KW - Depression
KW - GABA receptor
KW - Schizophrenia
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U2 - 10.1016/j.pharmthera.2012.08.006
DO - 10.1016/j.pharmthera.2012.08.006
M3 - Review article
C2 - 22921455
AN - SCOPUS:84867328459
VL - 136
SP - 142
EP - 152
JO - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
JF - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
SN - 0163-7258
IS - 2
ER -