Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, MA 02478, USA.
Pharmacol Ther. 2012 Nov;136(2):142-52. doi: 10.1016/j.pharmthera.2012.08.006. Epub 2012 Aug 18.
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.
GABA(A) 受体具有重要的生理功能，这一点已被药理学研究和基因靶向小鼠模型实验所揭示，并且是广泛使用的药物（如苯二氮䓬类药物）的作用靶点。在这篇综述中，我们总结了目前关于含 α2 的 GABA(A) 受体（约占所有 GABA(A) 受体的 15-20%）功能的知识。这种受体亚型介导地西泮的抗焦虑样、增强奖赏和抗痛觉过敏作用，并且具有抗抑郁样特性。含 α2 的 GABA(A) 受体的二级功能不足被认为在精神分裂症的发病机制中起作用，并且可能与其他疾病的认知障碍有关。此外，编码 GABA(A) 受体 α2 亚基的 GABRA2 基因的多态性已被发现与慢性酒精依赖和多药物滥用有关。因此，含 α2 的 GABA(A) 受体参与情绪行为和慢性疼痛的调节和/或调制，并且似乎是治疗焦虑症、抑郁症、精神分裂症和慢性疼痛的新型治疗方法的有效靶点。
