Antidepressant effects of esketamine via the BDNF/AKT/mTOR pathway in mice with postpartum depression and their offspring.
Han Qin, Miao Yu, Nianjiao Han, Meilin Zhu, Xia Li, Jing Zhou
Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2024 DOI: 10.1016/j.pnpbp.2024.110992 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice with postpartum depression and their offspring |
| Intervention | Esketamine |
| Topics | Esketamine Depression |
| Keywords | Bdnf/akt/mtor Postpartum depression ppd Postnatal depression Esketamine spravato Ketamine derivative Neuroscience brain chemistry Neural pathways |
| Citations | 27 |
| Key points | Esketamine ameliorated anxiety- and depression-like behaviors and restored impaired BDNF/AKT/mTOR signaling in the frontal and hippocampal regions of mice with PPD and their offspring. |
Abstract
Postpartum depression (PPD) is a serious mental health problem that can negatively affect future generations. BDNF/AKT/mTOR signaling in the frontal lobe and hippocampus in mice is associated with depression, but its role in mice with PPD and their offspring is unknown. This study was aimed at investigating the effects of esketamine (ESK), a drug approved for treatment of refractory depression, on the BDNF/AKT/mTOR pathway in mice with PPD and their offspring. A model of chronic unpredictable mild stress with pregnancy was used. ESK was injected into postpartum mice, and behavioral tests were conducted to predict the severity of symptoms at the end of lactation and in the offspring after adulthood. Both mice with PPD and their offspring showed significant anxiety- and depression-like behaviors that were ameliorated with the ESK intervention. ESK enhanced exploratory behavior in unfamiliar environments, increased the preference for sucrose, and ameliorated the impaired BDNF/AKT/mTOR signaling in the frontal and hippocampal regions in mice. Thus, ESK may have great potential in treating PPD and decreasing the incidence of depression in offspring.
Comparable studies
Other preclinical and animal studies on esketamine for depression, most cited first.
Citations in the library
Cited by 7
- Effect of esketamine on postoperative depression and anxiety in patients undergoing cardiac valve surgery: a randomised, placebo-controlled, double-blinded clinical trial. Pharmacological Research November 22, 2025
- Prophylactic esketamine for postpartum depression after cesarean section: a systematic review and meta-analysis. Journal of Affective Disorders June 10, 2025
- Modulating tonic NMDA receptor currents: mechanistic insights into ketamine, esketamine, and dextromethorphan for major depressive disorder and implications for the discovery and development of investigational agents. Expert Opinion on Therapeutic Targets January 28, 2026
- Multimodal rapid anti-depression: Esketamine combined with dexmedetomidine patient-controlled sleep for treatment-resistant depression - A retrospective study. Journal of Affective Disorders January 30, 2026
- S-ketamine mitigates paclitaxel-induced pain-related anxiety-like behavior through downregulation of mGluR5 and activation of the BDNF/TrkB signaling pathway Frontiers in Neurology April 23, 2026
and 2 more in the library
Cites 8
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
- The Antidepressant Actions of Ketamine and its Enantiomers Pharmacology & Therapeutics May 1, 2023
- Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants Translational Psychiatry September 20, 2016
- The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review Pharmaceutics December 22, 2023
and 3 more in the library