ArticleCellular and molecular neurobiology2023
S-Ketamine Exerts Antidepressant Effects by Regulating Rac1 GTPase Mediated Synaptic Plasticity in the Hippocampus of Stressed Rats.
Article in Cellular and molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Efficacy and safety of esketamine on major depression, postpartum depression and perioperative depression: a systematic review and meta-analysis.Molecular psychiatry · 2026Pooled it
- Effect of subanesthetic dose esketamine on anxiety and depression in patients with breast cancer after surgery: a randomized controlled, double-blind study.BMC psychiatry · 2026Trial
- Ascorbic acid enhances antidepressant-like efficacy of esketamine: Hippocampal TARP-γ8-containing AMPA receptors mediate synaptic modulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Esketamine in depression: putative biomarkers from clinical research.European archives of psychiatry and clinical neuroscience · 2025Review
- Research Progress on the Mechanism of Ketamine in Neuropathic Pain Comorbid Depression.Neuropsychiatric disease and treatment · 2025Review
- Ketamine induced synaptic plasticity operates independently of long-term potentiation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Targeting metaplasticity mechanisms to promote sustained antidepressant actions.Molecular psychiatry · 2024Review
- Early Astrocytic Dysfunction Is Associated with Mistuned Synapses as well as Anxiety and Depressive-Like Behavior in the AppNL-F Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Esketamine Inhibits Cocaine-Seeking Behaviour Subsequent to Various Abstinence Conditions in Rats.Biomolecules · 2023Article
- Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel.International journal of molecular sciences · 2023Review
- The antidepressant actions of ketamine and its enantiomers.Pharmacology & therapeutics · 2023Review
- The Antidepressant-like Activity and Cognitive Enhancing Effects of the Combined Administration of (Pharmaceuticals (Basel, Switzerland) · 2023Article
- Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review.Frontiers in psychiatry · 2023Article
- TIAM1-mediated synaptic plasticity underlies comorbid depression-like and ketamine antidepressant-like actions in chronic pain.The Journal of clinical investigation · 2022Article
- Postsynaptic Proteins at Excitatory Synapses in the Brain-Relationship with Depressive Disorders.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Clinical studies have found that ketamine has a rapid and lasting antidepressant effect, especially in the case of patients with major depressive disorder (MDD). The molecular mechanisms, however, remain unclear. In this study, we observe the effects of S-Ketamine on the expression of Rac1, neuronal morphology, and synaptic transmission function in the hippocampus of stressed rats. Chronic unpredictable mild stress (CUMS) was used to construct stressed rats. The rats were given a different regimen of ketamine (20 mg/kg, i.p.) and Rac1 inhibitor NSC23766 (50 µg, ICV) treatment. The depression-like behavior of rats was evaluated by sucrose preference test and open-field test. The protein expression of Rac1, GluA1, synapsin1, and PSD95 in the hippocampus was detected by Western blot. Pull-down analysis was used to examine the activity of Rac1. Golgi staining and electrophysiological study were used to observe the neuronal morphology and long-term potentiation (LTP). Our results showed that ketamine can up-regulate the expression and activity of Rac1; increase the spine density and the expression of synaptic-related proteins such as GluA1, Synapsin1, and PSD95 in the hippocampus of stressed rats; reduce the CUMS-induced LTP impairments; and consequently improve depression-like behavior. However, Rac1 inhibitor NSC23766 could have effectively reversed ketamine-mediated changes in the hippocampus of rats and counteracted its antidepressant effects. The specific mechanism of S-Ketamine's antidepressant effect may be related to the up-regulation of the expression and activity of Rac1 in the hippocampus of stressed rats, thus enhancing synaptic plasticity.
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Registered trials
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