GABA_A receptors mediate most of the fast inhibitory transmissions in the central nervous system. These receptors are pentameric complexes that exhibit high structural and pharmacological heterogeneity, as they can be constructed from 19 distinct subunits. GABA_A receptors are the targets of numerous clinically relevant drugs used to treat various disorders such as anxiety, insomnia and epilepsy. These receptors are also the targets of many volatile anesthetics and drugs of abuse, such as alcohol. This review is focused on the effect of long-term treatment with GABA, and the positive allosteric modulators benzodiazepines, neurosteroids and ethanol on GABA_A receptors. Prolonged exposure of GABA_A receptors to these compounds triggers several adaptive mechanisms that lead to changes in the structure, function and localization of receptors. These changes include GABA_A receptor subunit expression, intracellular trafficking and phosphorylation. These adaptations are relevant to different physiological, pathological and pharmacological conditions and, in most cases, are associated with the development of tolerance. Understanding the molecular mechanisms underlying these regulatory processes will be relevant for therapeutic benefits.

GABA _A受体介导大多数中枢神经系统的快速抑制性传递。这些受体是五聚体复合物，具有很高的结构和药理学异质性，因为它们可以由19个不同的亚基构建而成。GABA _A受体是许多用于治疗各种疾病（如焦虑症，失眠症和癫痫病）的临床相关药物的靶标。这些受体也是许多挥发性麻醉剂和滥用药物（例如酒精）的靶标。这篇综述的重点是长期使用GABA以及正变构调节剂苯并二氮杂卓，神经甾体和乙醇对GABA _A受体的影响。长时间接触GABA _A这些化合物的受体触发几种适应性机制，这些机制导致受体的结构，功能和位置发生变化。这些变化包括GABA _A受体亚基的表达，细胞内运输和磷酸化。这些适应症与不同的生理，病理和药理条件有关，并且在大多数情况下与耐受性的发展有关。了解这些调节过程的分子机制与治疗益处有关。