Ketamine Alleviates Depressive-Like Behaviors via Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice.
Si-Jie Tan, Yan Wang, Ke Chen, Zhi-Feng Long, Ju Zou
Biological and Pharmaceutical Bulletin August 1, 2017 DOI: 10.1248/bpb.b17-00131 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (mouse model of chronic restraint stress) Peer reviewed |
|---|---|
| Population | Mice exposed to chronic restraint stress |
| Intervention | Ketamine |
| Measures | Forced swimming test (FST), sucrose preference test (SPT) |
| Topics | Esketamine Ketamine |
| Key findings | Chronic restraint stress produced depressive-like behaviors in mice together with hippocampal inflammation (elevated IL-1β, TNF-α, IL-6, more reactive microglia, and up-regulated TLR4/p38 and P2X7 receptor). Ketamine treatment normalized these neurobehavioral and biochemical abnormalities, suggesting that down-regulation of pro-inflammatory cytokines may contribute to ketamine's antidepressant effects. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 23
- Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review Journal of Psychopharmacology June 26, 2021
- Brain region-specific action of ketamine as a rapid antidepressant. Science August 9, 2024
- Targeting inflammation in depression: Ketamine as an anti-inflammatory antidepressant in psychiatric emergency Brain, Behavior, & Immunity - Health November 1, 2021
- Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile Drug Discovery Today February 1, 2023
- Esketamine Prevents Postoperative Emotional and Cognitive Dysfunction by Suppressing Microglial M1 Polarization and Regulating the BDNF-TrkB Pathway in Ageing Rats with Preoperative Sleep Disturbance Molecular Neurobiology January 15, 2024
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