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Ketamine Alleviates Depressive-Like Behaviors via Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice
Open accessAbstract
The purpose of the present study was to investigate whether ketamine's rapid antidepressant effects were associated with its anti-inflammatory actions and to explore the underlying molecular mechanism. Depressive-like behaviors was induced in mice using chronic restraint stress (CRS) method. Anti-depressive effects of ketamine were evaluated by forced swimming tests (FST) and sucrose preference test (SPT). Subsequently, brain tissue was harvested to investigate inflammatory response in the hippocampus via investigating reactive microglia numbers, serum cytokines levels and the toll-like receptor type 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) pathway. CRS exposure caused depressive-like behaviors in mice, which was associated with increased pre-inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6) levels, reactive microglia numbers and up-regulated regulatory molecules such as TLR4/p38 and P2X7 receptor in hippocampus. Such neurobehavioral and biochemical abnormalities were normalized by ketamine treatment. CRS-induced depression-like behaviours are associated with activation of hippocampal inflammatory response, whereas down-regulation of pro-inflammatory cytokines may contribute to ketamine's antidepressant effects in mice.
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“Moreover, the antidepressant-like effect induced by clemasine [80] and ketamine [81] were associated with decreased hippocampal P2X7R levels in the in stressed mice.”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [81]
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“and exposure of mice to chronic restraint stress (CRS) increased hippocampal P2X7R levels [81].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [81]
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Metadata
- Authors
- Tan, S., Wang, Y., Chen, K., Long, Z., & Zou, J.
- Affiliations
- University of South China (CN)
- Venue
- Biological & Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2017
- Volume
- 40
- Issue
- 8
- Pages
- 1260-1267
- ISSN
- 0918-6158 (ISSN-L)
- 1347-5215
- OpenAlex
- W2741144353
- Cited by
- 142
- References
- 42
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 10 · 2023: 19 · 2022: 23 · 2021: 19 · 2020: 19 · 2019: 20 · 2018: 12 · 2017: 1
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Biological and Pharmaceutical Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of South China
- Construct Program of the Key Discipline in Hunan Province
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- ketamine, rapid antidepressant effects, chronic restraint stress, depression-like behavior, neuroinflammation, hippocampus, microglial activation, inflammatory cytokines, P2X7 receptor, IL-1β, TNF-α, interleukin-6, antidepressant mechanism
- MeSH terms
- Animals, Antidepressive Agents, Behavior, Animal, Corticosterone, Food Preferences, Hippocampus, Ketamine, Restraint, Physical, Stress, Psychological, Sucrose, Swimming, Down-Regulation, Cytokines, Excitatory Amino Acid Antagonists, p38 Mitogen-Activated Protein Kinases, Toll-Like Receptor 4, Mice, Receptors, Purinergic P2X7
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