Over the past six decades, the use of ketamine has evolved from an anesthetic and recreational drug to the first non-monoaminergic antidepressant approved for treatment-resistant major depressive disorder (MDD). Subanesthetic doses of ketamine and its enantiomer (S)-ketamine (esketamine) directly bind to several neurotransmitter receptors [including N-methyl-d-aspartic acid receptor (NMDAR), κ and μ opioid receptor (KOR and MOR)] widely distributed in the brain and across different cell types, implicating several potential molecular mechanisms underlying the action of ketamine as an antidepressant. This review examines preclinical studies investigating cell-type-specific mechanisms underlying the effects of ketamine on behavior and synapses. Cell-type-specific approaches are crucial for disentangling the critical mechanisms involved in the therapeutic effect of ketamine.

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氯胺酮抗抑郁作用的细胞类型特异性机制的综合观点

在过去的六十年里，氯胺酮的使用已经从一种麻醉剂和娱乐药物发展成为第一种被批准用于治疗难治性重度抑郁症（MDD）的非单胺能抗抑郁药。亚麻醉剂量的氯胺酮及其对映体 (S)-氯胺酮 (esketamine) 直接与多种神经递质受体 [包括 N-甲基-d-天冬氨酸受体 (NMDAR)、κ 和 μ 阿片受体 (KOR 和 MOR)] 广泛分布于大脑和不同细胞类型之间的关系，暗示了氯胺酮作为抗抑郁药作用的几种潜在分子机制。本综述回顾了临床前研究，调查了氯胺酮对行为和突触影响的细胞类型特异性机制。细胞类型特异性方法对于解开氯胺酮治疗作用中涉及的关键机制至关重要。