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Low-dose S-ketamine exerts antidepressant-like effects via enhanced hippocampal synaptic plasticity in postpartum depression rats.

Zhuoyu Ren, Mingling Wang, Mokhtar Aldhabi, Rui Zhang, Yongxin Liu, Shaoyan Liu, Rundong Tang, Zuolei Chen

Neurobiology of Stress 2022 DOI: 10.1016/j.ynstr.2021.100422 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal study Peer reviewed
Population Rat model of postpartum depression induced by reproductive hormone withdrawal
Intervention S-ketamine
Dose low-dose
Topics Esketamine Neuroplasticity Depression Ketamine
Keywords Electrophysiology Hippocampi Postpartum depression
Citations 28
Key points Low-dose S-ketamine reduces depression- and anxiety-like behaviors and maintains hippocampal synaptic plasticity in a rat model of postpartum depression.

Abstract

Rapid antidepressant effects of S-ketamine have repeatedly been confirmed in patients with depression, as well as in chronic unpredictable mild stress (CUMS) animal models. However, the pharmacological study of S-ketamine for anti-postpartum depression has not been considered. In this study, the classical method of reproductive hormone withdrawal was used to construct a rat model of postpartum depression (PPD). Subsequently, the study evaluated the effects of low-dose S-ketamine on behavior and synaptic plasticity, which is related to depression, in the hippocampus of PPD rats. Multiple behavioral tests were used to evaluate depression-like behaviors in PPD models. Synaptic plasticity of the hippocampus can be demonstrated by Western blot, Golgi staining, transmission electron microscopy, and electrophysiological recording. Our study provides insight into the role of low-dose S-ketamine in antidepressant as well as antianxiety and indicates that maintaining synaptic plasticity is a key target for S-ketamine therapy for postpartum depression induced by reproductive hormone withdrawal.

Comparable studies

Other preclinical and animal studies on esketamine for depression, most cited first.

Study Year Design Participants
Antidepressant effects of esketamine via the BDNF/AKT/mTOR pathway in mice with postpartum depression and their offspring. Mice with postpartum depression and their offspring 2024 Animal study
Electroconvulsive therapy combined with esketamine improved depression through PI3K/AKT/GLT-1 pathway. Human patients with severe depression and a rat model of depression 2025 Randomized controlled trial and animal study n = 12
S-ketamine Alleviates Neuroinflammation and Attenuates Lipopolysaccharide-Induced Depression Via Targeting SIRT2. Lipopolysaccharide (LPS)-induced mouse model 2025 Animal study with in vitro and in vivo experiments
Esketamine alleviates LPS-induced depression-like behavior by activating Nrf2-mediated anti-inflammatory response in adolescent mice. Adolescent male C57BL/6J mice 2025 Preclinical experimental study
S-ketamine alleviates depression-like behavior and hippocampal neuroplasticity in the offspring of mice that experience prenatal stress. Male offspring of pregnant rats subjected to chronic unpredictable mild stress 2024 Animal study

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