Role of the mTOR signaling pathway in the rapid antidepressant action of ketamine
Abstract
Some patients with major depressive disorder remain resistant to antidepressant medication. A randomized, placebo-controlled, double-blind trial demonstrated that a single subanesthetic dose (0.5 mg/kg) of the N-methyl-D-aspartate receptor antagonist ketamine caused a rapid antidepressant effect within hours in treatment-resistant patients with major depressive disorder. However, the precise cellular mechanisms underlying ketamine's rapid antidepressant actions were unclear, although it is proposed that the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor might be involved in these mechanisms. Recently, Li et al. reported the role of the mammalian target of rapamycin (mTOR) signaling pathway, a ubiquitous protein kinase involved in protein synthesis and synaptic plasticity, in ketamine's rapid antidepressant effects. Here, these findings are put into context and their significance is discussed.
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Ketamine produces antidepressant response by rapidly inducing synaptic plasticity in neuronal networks.
“This drug produces AD response by rapidly inducing synaptic plasticity in neuronal networks [28,29,30].”
From The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes (2023) · cites this paper as [29]
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BDNF activates mTOR to regulate GluR1 expression required for memory formation
Slipczuk, L., Bekinschtein, P., Katche, C., Cammarota, M., Izquierdo, I., & Medina, J. H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006007 · Cited by 246 · see citing works
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Zhang, J.-C., Yao, W., & Hashimoto, K. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160119094646 · Cited by 538 · see citing works
Self-citationThe mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder
Jernigan, C. S., Goswami, D. B., Austin, M. C., Iyo, A. H., Chandran, A., Stockmeier, C. A., & Karolewicz, B. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.05.010 · Cited by 386 · see citing works
Hashimoto, K. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12902 · Cited by 335 · see citing works
Self-citationZhang, J.-C., Wu, J., Fujita, Y., Yao, W., Ren, Q., Yang, C., Li, S.-X., Shirayama, Y., & Hashimoto, K. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu077 · Cited by 289 · see citing works
Self-citationmTOR-Dependent Cell Proliferation in the Brain
Ryskalin, L., Lazzeri, G., Flaibani, M., Biagioni, F., Gambardella, S., Frati, A., & Fornai, F. (2017) · BioMed Research International · doi:10.1155/2017/7082696 · Cited by 86 · see citing works
Yang, C., Li, W.-Y., Yu, H.-Y., Gao, Z.-Q., Liu, X.-L., Zhou, Z.-Q., & Yang, J.-J. (2012) · Journal of Biomedicine and Biotechnology · doi:10.1155/2012/175619 · Cited by 29 · see citing works
Santos, M., Lima, L., Carvalho, S., Mota-Pereira, J., Pimentel, P., Maia, D., Correia, D., Barroso, M. F., Gomes, S., Cruz, A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076758 · Cited by 20 · see citing works
- Authors
- Hashimoto, K.
- Affiliations
- Chiba University (JP)
- Corresponding author
- Hashimoto, Kenji
- ORCID
- Hashimoto, Kenji
- Venue
- Expert Review of Neurotherapeutics
- Publisher
- Informa UK Limited
- Published
- 2011-01
- Volume
- 11
- Issue
- 1
- Pages
- 33-36
- ISSN
- 1473-7175 (ISSN-L)
- 1744-8360
- OpenAlex
- W2069204031
- Cited by
- 47
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Review of Neurotherapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ketamine, mTOR signaling, rapid antidepressant effects, treatment-resistant depression, major depressive disorder, NMDA receptor antagonists, AMPA receptors, synaptic plasticity, protein synthesis, antidepressant mechanism
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