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

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.