The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism
Open accessAbstract
The molecular mechanisms underlying major depressive disorder remain poorly understood, and current antidepressant treatments have many shortcomings. The recent discovery that a single intravenous infusion of ketamine at a subanesthetic dose had robust, rapid and sustained antidepressant effects in individuals with treatment-resistant depression inspired tremendous interest in investigating the molecular mechanisms mediating ketamine’s clinical efficacy as well as increased efforts to identify new targets for antidepressant action. We review the clinical utility of ketamine and recent insights into its mechanism of action as an antidepressant, including the roles of N-methyl-d-aspartate receptor inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor upregulation, activation of downstream synaptogenic signalling pathways and the production of an active ketamine metabolite, hydroxynorketamine. Emerging knowledge of the molecular mechanisms underlying both ketamine’s positive therapeutic and detrimental side effects will aid the development of a new generation of much-needed superior antidepressant agents.
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“TrkB activation triggers ERK and mTORC1 cascades, extends protein synthesis windows, and supports dendritic spine maturation”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [339]
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“Ketamine and psychedelics activate cortical AMPAR and subsequently stimulate BDNF and synaptic efficacy (111).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [111]
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Cites
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,525
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li, N., Lee, B., Liu, R.-J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2010) · Science · doi:10.1126/science.1190287 · Cited by 2,881
NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses
Autry, A. E., Adachi, M., Nosyreva, E., Na, E. S., Los, M. F., Cheng, P.-F., Kavalali, E. T., & Monteggia, L. M. (2011) · Nature · doi:10.1038/nature10130 · Cited by 1,926
Moghaddam, B., Adams, B., Verma, A., & Daly, D. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-08-02921.1997 · Cited by 1,793
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016) · Nature Medicine · doi:10.1038/nm.4050 · Cited by 1,750
Synaptic Dysfunction in Depression: Potential Therapeutic Targets
Duman, R. S., & Aghajanian, G. K. (2012) · Science · doi:10.1126/science.1222939 · Cited by 1,651
NMDAR inhibition-independent antidepressant actions of ketamine metabolites
Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., Alkondon, M., Yuan, P., Pribut, H. J., Singh, N. S., et al. (2016) · Nature · doi:10.1038/nature17998 · Cited by 1,609
Maeng, S., Zarate, C. A., Du, J., Schloesser, R. J., McCammon, J., Chen, G., & Manji, H. K. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.028 · Cited by 1,103
Li, N., Liu, R.-J., Dwyer, J. M., Banasr, M., Lee, B., Son, H., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.015 · Cited by 1,082
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Research works printed but not linked: 3
- Huynh NN, 2008, Prim Care Companion J Clin Psychiatry, 10, 91
- 10.1016/j.pneuro-bio.2015.12.001 · DOI
- Yang B, 2016, Psychopharmacology (Berl)
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Dendritic structural plasticity and neuropsychiatric disease
Forrest, M. P., Parnell, E., & Penzes, P. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.16 · Cited by 464
Tartt, A. N., Mariani, M. B., Hen, R., Mann, J. J., & Boldrini, M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01520-y · Cited by 408
“The dorsolateral prefrontal cortex (DLPFC) is responsible for attention, working memory and executive function and is positively correlated with working memory load in healthy controls [36].”
BackgroundInfluentialBahji, A., Vazquez, G. H., & Zarate, C. A. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.09.071 · Cited by 408
Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics
Aleksandrova, L. R., & Phillips, A. G. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.08.003 · Cited by 276
Self-citationde Vos, C. M. H., Mason, N. L., & Kuypers, K. P. C. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.724606 · Cited by 269
Metadata
- Authors
- Aleksandrova, L. R., Phillips, A. G., & Wang, Y. T.
- Affiliations
- University of British Columbia (CA)
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2017-07
- Volume
- 42
- Issue
- 4
- Pages
- 222-229
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC5487269
- OpenAlex
- W2628731659
- Cited by
- 228
- References
- 63
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 20 · 2023: 29 · 2022: 35 · 2021: 31 · 2020: 31 · 2019: 16 · 2018: 14 · 2017: 7
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › 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
- ketamine, antidepressant mechanism, major depressive disorder, treatment-resistant depression, NMDA receptor antagonism, AMPA receptors, hydroxynorketamine, ketamine side effects, antidepressant drug development
- MeSH terms
- Animals, Antidepressive Agents, Depression, Humans, Ketamine, Models, Neurological, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA
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