谷氨酸的
单胺类
γ-氨基丁酸受体
神经科学
抗抑郁药
神经活性类固醇
加巴能
心理学
神经传递
兴奋性突触后电位
认知
抑制性突触后电位
医学
受体
谷氨酸受体
内科学
海马体
血清素
作者
Bernhard Lüscher,Jamie Maguire,Uwe Rudolph,Etienne Sibille
标识
DOI:10.1016/j.tips.2023.06.009
摘要
In the past 20 years, our understanding of the pathophysiology of depression has evolved from a focus on an imbalance of monoaminergic neurotransmitters to a multifactorial picture including an improved understanding of the role of glutamatergic excitatory and GABAergic inhibitory neurotransmission. FDA-approved treatments targeting the glutamatergic [esketamine for major depressive disorder (MDD)] and GABAergic (brexanolone for peripartum depression) systems have become available. This review focuses on the GABAA receptor (GABAAR) system as a target for novel antidepressants and discusses the mechanisms by which modulation of δ-containing GABAARs with neuroactive steroids (NASs) or of α5-containing GABAARs results in antidepressant or antidepressant-like actions and discusses clinical data on NASs. Moreover, a potential mechanism by which α5-GABAAR-positive allosteric modulators (PAMs) may improve cognitive deficits in depression is presented.
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