(R)-Ketamine Rapidly Ameliorates the Decreased Spine Density in the Medial Prefrontal Cortex and Hippocampus of Susceptible Mice After Chronic Social Defeat Stress
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Background: A recent study demonstrated that spine formation rates by ketamine in the prefrontal cortex (PFC) were not altered at 3–6 h following a single injection, but were markedly altered at 12–24 h. Here, we investigated the acute (3 h post-treatment) effects of (R)-ketamine in the decreased spine density in the medial PFC (mPFC) and hippocampus in susceptible mice after chronic social defeat stress (CSDS). Methods: (R)-ketamine (10 mg/kg) or saline was administered intraperitoneally to CSDS-susceptible mice. Dendritic spine density in the mPFC and hippocampus was measured 3 h after a single injection. Results: (R)-ketamine significantly ameliorated the decreased spine density in the prelimbic area of mPFC, Cornu Ammonis3, and dentate gyrus of the hippocampus of CSDS-susceptible mice Conclusions: This study suggests that (R)-ketamine rapidly ameliorates the decreased spine density in the mPFC and hippocampus of CSDS-susceptible mice, resulting in its rapid-acting antidepressant effects.
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Cortical neuron atrophy and dysfunction is observed in rodents following chronic corticosterone administration, chronic unpredictable mild stress, chronic restraint stress, and chronic social defeat stress.
“Cortical neuron atrophy and dysfunction is observed in rodents following chronic corticosterone administration (121), chronic unpredictable mild stress (122, 123), chronic restraint stress (48, 49, 124, 125), and chronic social defeat stress (126–128).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [128]
The Results (page not provided) report significantly lower dendritic spine density in the prelimbic medial prefrontal cortex of mice susceptible to chronic social defeat stress, supporting a specific cortical structural change. The paper does not establish cortical neuron dysfunction or generalized cortical neuron atrophy, and this citation is attached only to the social-defeat-stress portion of the sentence. (LLM, conf=0.86)
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Yao, W., Cao, Q., Luo, S., He, L., Yang, C., Chen, J., Qi, Q., Hashimoto, K., & Zhang, J.-C. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01377-7 · Cited by 216 · see citing works
Self-citationYang, C., Yang, J., Luo, A., & Hashimoto, K. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0624-1 · Cited by 190 · see citing works
Self-citationPsychedelics and Other Psychoplastogens for Treating Mental Illness.
Vargas, M. V., Meyer, R., Avanes, A. A., Rus, M., & Olson, D. E. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.727117 · Cited by 166 · see citing works
How do serotonergic psychedelics treat depression: The potential role of neuroplasticity
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- Authors
- Zhang, J., Qu, Y., Chang, L., Pu, Y., & Hashimoto, K.
- Affiliations
- Chiba University (JP)
- Corresponding author
- Hashimoto, Kenji
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-09-01
- Volume
- 22
- Issue
- 10
- Pages
- 675-679
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC6822137
- OpenAlex
- W2970142577
- Cited by
- 55
- References
- 5
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 5 · 2023: 7 · 2022: 17 · 2021: 8 · 2020: 4 · 2019: 1
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development (JP19dm0107119)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- (R)-ketamine, chronic social defeat stress, dendritic spine density, medial prefrontal cortex, hippocampus, rapid-acting antidepressants, depression, stress vulnerability, prelimbic cortex, dentate gyrus, NMDA receptor antagonists
- MeSH terms
- Animals, Hippocampus, Ketamine, Male, Social Behavior, Stress, Psychological, Prefrontal Cortex, Dendritic Spines, Mice
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