ArticleBipolar disorders2016
Ketamine-induced inhibition of glycogen synthase kinase-3 contributes to the augmentation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor signaling.
Article in Bipolar disorders, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity.Frontiers in psychiatry · 2022Pooled it
- BDNF and GSK-3β signaling in depression: molecular mechanisms underlying neural plasticity dysfunction.Molecular biology reports · 2026Review
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Membrane Trafficking in Psychiatric Disorders: Bridging Cellular Dysfunction and Mental Health-A Narrative Review.Molecular neurobiology · 2025Review
- Adverse Effects Associated With High-Dose Ketamine Infusions For Refractory Pain And Psychiatric Conditions.Current pain and headache reports · 2025Review
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Preclinical models of treatment-resistant depression: challenges and perspectives.Pharmacological reports : PR · 2023Review
- Linking Hypothermia and Altered Metabolism with TrkB Activation.ACS chemical neuroscience · 2023Article
- Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression.Frontiers in neuroscience · 2023Review
- Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review.Frontiers in psychiatry · 2023Article
- Review
- GSK-3β Disrupts Neuronal Oscillatory Function to Inhibit Learning and Memory in Male Rats.Cellular and molecular neurobiology · 2022Article
- The role of serotonin neurotransmission in rapid antidepressant actions.Psychopharmacology · 2022Review
- Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications.Neuroscience bulletin · 2021Review
- Ketamine-50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms.Pharmacological reports : PR · 2021Review
- Ketamine: A tale of two enantiomers.Journal of psychopharmacology (Oxford, England) · 2021Review
- A Multiscale View of the Mechanisms Underlying Ketamine's Antidepressant Effects: An Update on Neuronal Calcium Signaling.Frontiers in behavioral neuroscience · 2021Review
- Ketamine: Neuroprotective or Neurotoxic?Frontiers in neuroscience · 2021Review
- Glycogen synthase kinase-3 inhibition rescues sex-dependent contextual fear memory deficit in human immunodeficiency virus-1 transgenic mice.British journal of pharmacology · 2020Article
- Sex and chronic stress alter delta opioid receptor distribution within rat hippocampal CA1 pyramidal cells following behavioral challenges.Neurobiology of stress · 2020Article
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5 authors at 1 institution in 1 country.
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Abstract
objectivesSub-anesthetic doses of ketamine have been found to provide rapid antidepressant actions, indicating that the cellular signaling systems targeted by ketamine are potential sites for therapeutic intervention. Ketamine acts as an antagonist of N-methyl-D-aspartate (NMDA) receptors, and animal studies indicate that subsequent augmentation of signaling by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors is critical for the antidepressant outcome.
methodsIn this study, we tested if the inhibitory effect of ketamine on glycogen synthase kinase-3 (GSK3) affected hippocampal cell-surface AMPA receptors using immunoblotting of membrane and synaptosomal extracts from wild-type and GSK3 knockin mice.
resultsTreatment with an antidepressant dose of ketamine increased the hippocampal membrane level of the AMPA glutamate receptor (GluA)1 subunit, but did not alter the localization of GluA2, GluA3, or GluA4. This effect of ketamine was abrogated in GSK3 knockin mice expressing mutant GSK3 that cannot be inhibited by ketamine, demonstrating that ketamine-induced inhibition of GSK3 is necessary for up-regulation of cell surface AMPA GluA1 subunits. AMPA receptor trafficking is regulated by post-synaptic density-95 (PSD-95), a substrate for GSK3. Ketamine treatment decreased the hippocampal membrane level of phosphorylated PSD-95 on Thr-19, the target of GSK3 that promotes AMPA receptor internalization.
conclusionsThese results demonstrate that ketamine-induced inhibition of GSK3 causes reduced phosphorylation of PSD-95, diminishing the internalization of AMPA GluA1 subunits to allow for augmented signaling through AMPA receptors following ketamine treatment.
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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.