ArticleScience (New York, N.Y.)2025
Enhanced ERK activity extends ketamine's antidepressant effects by augmenting synaptic plasticity.
Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed.
- GATA3 drives chronic stress-induced depressive-like behaviors by reducing hippocampal CA3 pyramidal neuronal activity in male mice.Acta pharmacologica Sinica · 2026Article
- [(Es)ketamine: practice update].Der Nervenarzt · 2026Review
- From Biomarkers to New Treatments for Post-Traumatic Stress Disorder.Neuroscience bulletin · 2026Review
- Emerging Molecular Targets and Recent Advancements for the Management of Depression.Molecular neurobiology · 2026Review
- NADPH oxidase-1 suppression prolongs the antidepressant-like effect of ketamine.Molecular psychiatry · 2026Article
- Linking GWAS risk genes to transcriptional features of major depressive disorder via in vivo Perturb-seq.Nature genetics · 2026Article
- A brain-enriched circRNA blood biomarker can predict response to SSRI antidepressants.Molecular psychiatry · 2026Article
- Review
- Intermittent Ketamine and Neuromodulation Treatment Evoke Synergistic Antidepressant-Relevant Action.Biological psychiatry · 2026Article
- Synaptojanin-2-binding protein ameliorates oxidative stress, neuroinflammation and depression-like behaviors via SYNJ2/PIPRedox biology · 2026Article
- Rapid antidepressant potential of nitrous oxide: current state and major questions.Molecular psychiatry · 2026Review
- TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine.Science advances · 2026Article
- A Time-Sensitive Plasticity Distinguishes the Rapid and Sustained Synaptic Actions of Ketamine from Its (2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Cortical Mechanisms Contributing to Ketamine-Induced Dissociation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- The hippocampus as a central hub in ketamine's antidepressant action: from molecules to circuit rewiring.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- An Overview of Depression Pathogenesis: Prevailing Hypotheses and Associated Neurobiological Underpinnings Primarily Evidenced by Rodent Studies.Depression and anxiety · 2026Review
- Therapeutic Potentials of Anesthetics.Current neuropharmacology · 2026Article
- Intestinal γδ T17-IL-17A signaling disrupts hippocampal mitophagy in stress-induced depression and is restored by arketamine.Journal of neuroinflammation · 2025Article
- The NMDA receptor subunit GluN2D is a potential target for rapid antidepressant action.Nature communications · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
Repeated ketamine treatment to maintain a rapid antidepressant effect can lead to side effects over time, highlighting an unmet clinical need for sustaining this drug's antidepressant action from a single administration. Ketamine-induced synaptic potentiation at CA3-CA1 synapses has been proposed to be a key synaptic substrate for antidepressant action. Here, we found that ketamine-induced CA3-CA1 synaptic potentiation could be augmented by transiently increasing extracellular signal-regulated kinase (ERK) activity through pharmacological inhibition of dual-specificity phosphatases 6 (DUSP6). The antidepressant-like behavioral effects of acute ketamine treatment were extended by DUSP6 inhibition for up to 2 months. The selective deletion of tropomyosin receptor kinase B (TrkB) in excitatory neurons abolished these DUSP6 inhibition-mediated synaptic and behavioral effects. These data suggest that ketamine's rapid antidepressant effects can be sustained by selectively targeting downstream intracellular signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.