Role of Inflammatory Bone Markers in the Antidepressant Actions of (R)-Ketamine in a Chronic Social Defeat Stress Model
Kai Zhang, Min Ma, Chao Dong, Kenji Hashimoto
The International Journal of Neuropsychopharmacology July 17, 2018 DOI: 10.1093/ijnp/pyy065 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Chronic social defeat stress-susceptible mice |
| Interventions | (R)-ketamine (S)-ketamine |
| Topics | Esketamine Ketamine |
| Citations | 30 |
| Key points | (R)-ketamine showed more potent antidepressant-like behavioral effects than (S)-ketamine in chronically stressed mice, and (R)-ketamine but not (S)-ketamine significantly attenuated elevated plasma receptor activator of nuclear factor κB ligand. Sucrose preference correlated positively with the osteoprotegerin/receptor activator of nuclear factor κB ligand ratio, which the authors propose indicates inflammatory bone markers may play a role in (R)-ketamine's antidepressant effects. |
Abstract
Background: A recent study demonstrated that inflammatory bone markers play a role in the antidepressant functions of (R,S)-ketamine in treatment-resistant patients with depression. We examined the effect of inflammatory bone markers in the antidepressant functions of (R)-ketamine and (S)-ketamine in a chronic social defeat stress model.
Methods: Behavioral tests for antidepressant actions were performed after a single administration of (R)-ketamine or (S)-ketamine. We measured inflammatory bone marker levels in the plasma, which included osteoprotegerin, receptor activator of nuclear factor κB ligand, and osteopontin.
Results: (R)-ketamine's antidepressant effects were more potent than those of (S)-ketamine in the behavioral tests. Furthermore, (R)-ketamine but not (S)-ketamine significantly attenuated increased plasma levels of receptor activator of nuclear factor κB ligand in chronic social defeat stress-susceptible mice. We found a positive correlation between sucrose preference and osteoprotegerin/receptor activator of nuclear factor κB ligand ratio.
Conclusions: Our findings demonstrate that inflammatory bone markers may play a role in the antidepressant effects of (R)-ketamine.
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 14
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- An update on ketamine and its two enantiomers as rapid-acting antidepressants Expert Review of Neurotherapeutics December 4, 2018
- The Antidepressant Actions of Ketamine and its Enantiomers Pharmacology & Therapeutics May 1, 2023
- (R)-Ketamine Rapidly Ameliorates the Decreased Spine Density in the Medial Prefrontal Cortex and Hippocampus of Susceptible Mice After Chronic Social Defeat Stress The International Journal of Neuropsychopharmacology August 28, 2019
and 9 more in the library
Cites 10
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Psychological Medicine February 12, 2016
- Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model. Biological Psychiatry 2018
- Possible role of the gut microbiota–brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model Translational Psychiatry December 15, 2017
and 5 more in the library