Essential roles of AMPA receptor GluA1 phosphorylation and presynaptic HCN channels in fast-acting antidepressant responses of ketamine
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Ketamine alters presynaptic channels in the hippocampus to mediate fast-acting antidepressant action.
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Ketamine 20 μM enhanced GluA1 S845 phosphorylation at mouse SC-CA1 for up to two hours, and ketamine 10 mg/kg i.p. rapid and 7-day antidepressant-like effects were blocked in mice with an S845-to-alanine mutation.
“A study found that ketamine (20 μM bath application) enhances phosphorylation of GluA1 S845 at the SC-CA1 synapse of mice up to two hours post-treatment and its rapid (30 minutes) and long-term (7 days) antidepressant-like effects in the forced swim test (10 mg/kg i.p.) are blocked in mice with S845 mutated to an alanine residue that cannot be phosphorylated”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Zhang et al., 2016
The Results sections on GluA1 phosphorylation and S845A mice report that bath-applied ketamine increased Ser845 phosphorylation in hippocampal CA1 tissue and that ketamine reduced forced-swim immobility in wild-type mice but not S845A mice (page unavailable). The phosphorylation experiments described there used rat slices, not mouse slices; our copy reports an effect as early as 15 minutes but does not establish the claimed 20 μM dose or persistence for two hours. The S845A results do not establish forced-swim effects at both 30 minutes and seven days, or the specified 10 mg/kg dose. (LLM, conf=0.89)
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Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery
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- Authors
- Zhang, K., Xu, T., Yuan, Z., Wei, Z., Yamaki, V. N., Huang, M., Huganir, R. L., & Cai, X.
- Affiliations
- Southern Illinois University Carbondale (US)
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- Department of Physiology, Southern Illinois University School of Medicine, 1135 Lincoln Drive, Carbondale, IL 62901, USA.
- Howard Hughes Medical Institute (US)
- Corresponding author
- Xu, Ting
- Yuan, Zhongmin
- Wei, Zhisheng
- Cai, Xiang
- Venue
- Science Signaling
- Published
- 2016-12-13
- Volume
- 9
- Issue
- 458
- Pages
- ra123-ra123
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC5564288
- OpenAlex
- W2565604828
- Cited by
- 98
- References
- 49
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 13 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 16 · 2018: 20 · 2017: 7
- FWCI
- 11.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (NIHMH086828)
- Southern Illinois University School of Medicine (501871)
- National Natural Science Foundation of China (81271488, 81671339)
- Science and Technology Program of Guangzhou, China (2014Y2-00096)
- Foundation for High-level Talents in Higher Education of Guangdong, China (310109-012)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ketamine, rapid-acting antidepressants, AMPA receptors, GluA1 phosphorylation, HCN channels, NMDA receptor, hippocampus, synaptic transmission, glutamate release, behavioral despair
- MeSH terms
- Animals, Ketamine, Phosphorylation, Synapses, Potassium Channels, Rats, Sprague-Dawley, Pyramidal Cells, Receptors, AMPA, Mice, Knockout, Rats, CA1 Region, Hippocampal, CA3 Region, Hippocampal, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
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