Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice
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The actions of ketamine require inhibition of glycogen synthase kinase 3.
“The actions of ketamine also require inhibition of GSK3 (52).”
From Synaptic Dysfunction in Depression: Potential Therapeutic Targets (2012) · cites this paper as [52]
The paper reports that GSK3 inhibition is necessary for ketamine’s rapid antidepressant-like effect in a mouse learned-helplessness model. The citing sentence says “the actions of ketamine” without limiting the claim to that effect or model; the paper does not establish that all of ketamine’s actions require GSK3 inhibition. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSeveral intracellular signaling pathways, in addition to eEF2 kinase signaling, such as mTOR and GSK-3 have been implicated in the antidepressant effects of ketamine.
“Several intracellular signaling pathways, in addition to eEF2 kinase signaling, such as mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 (GSK-3) have been implicated in the antidepressant effects of ketamine (Beurel et al., 2011; Li et al., 2010).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Beurel et al., 2011
Inhibition of glycogen synthase kinase 3, which is required for the actions of ketamine in rodent models, could produce rapid ketamine-like effects or enhance the response to ketamine.
“Inhibition of GSK3, which is required for the actions of ketamine in rodent models (52), could also produce rapid ketamine-like effects or enhance the response to ketamine.”
From Synaptic Dysfunction in Depression: Potential Therapeutic Targets (2012) · cites this paper as [52]
Lithium has an antidepressant effect in the learned helplessness paradigm.
“lithium, which has an antidepressant effect in the learned helplessness paradigm (36)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [36]
Mice harboring a knock-in mutation at both GSK-3α and GSK-3β genes, which prevents the phosphorylation-dependent inactivation of the kinase, do not manifest ketamine-induced antidepressant behavioral responses.
“Mice harboring a knock-in mutation at both GSK-3α and GSK-3β genes, which prevents the phosphorylation-dependent inactivation of the kinase, do not manifest ketamine-induced antidepressant behavioral responses 186.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [186]
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- Authors
- Beurel, E., Song, L., & Jope, R. S.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Jope, R S
- ORCID
- Beurel, E
- Venue
- Molecular Psychiatry
- Published
- 2011-04-19
- Volume
- 16
- Issue
- 11
- Pages
- 1068-1070
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3200424
- OpenAlex
- W2061711185
- Cited by
- 288
- References
- 10
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 9 · 2023: 13 · 2022: 15 · 2021: 22 · 2020: 25 · 2019: 20 · 2018: 19 · 2017: 16 · 2016: 27 · 2015: 28 · 2014: 22 · 2013: 25 · 2012: 18
- FWCI
- 17.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K99MH090236, R01MH038752)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- glycogen synthase kinase-3, ketamine, rapid antidepressant effects, antidepressant mechanism, glycogen synthase kinase-3 inhibition
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Antidepressive Agents, Cerebral Cortex, Depression, Disease Models, Animal, Drug Evaluation, Preclinical, Electroshock, Helplessness, Learned, Hippocampus, Ketamine, Nerve Tissue Proteins, Phosphorylation, Phosphoserine, Protein Processing, Post-Translational, Point Mutation, Lithium Chloride, Amino Acid Substitution, Glycogen Synthase Kinase 3, Mice, Gene Knock-In Techniques
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