Beneficial effects of (R)-ketamine, but not its metabolite (2R,6R)-hydroxynorketamine, in the depression-like phenotype, inflammatory bone markers, and bone mineral density in a chronic social defeat stress model.
Zhongwei Xiong, Yuko Fujita, Kai Zhang, Yaoyu Pu, Lijia Chang, Min Ma, Jincao Chen, Kenji Hashimoto
Behavioural Brain Research August 1, 2019 DOI: 10.1016/j.bbr.2019.111904 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice susceptible to chronic social defeat stress |
| Interventions | (R)-ketamine (2R 6R)-hydroxynorketamine |
| Topics | Depression Esketamine Ketamine |
| Key findings | (R)-ketamine, but not (2R,6R)-HNK, elicited rapid and sustained antidepressant effects and improved inflammatory bone markers and bone mineral density in CSDS susceptible mice. |
Abstract
Inflammatory bone markers may play a role in the antidepressant actions of (R)-ketamine in susceptible mice after chronic social defeat stress (CSDS). In this study, we compared the effects of (R)-ketamine and its final metabolite (2R,6R)-hydroxynorketamine (HNK) in depression-like phenotypes, inflammatory bone markers and bone mineral density (BMD) in CSDS susceptible mice. We measured plasma levels of inflammatory bone markers, which included osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), and osteopontin after behavioral tests. (R)-ketamine, but not (2R,6R)-HNK, elicited rapid and sustained antidepressant effects in CSDS susceptible mice. Furthermore, (R)-ketamine, but not (2R,6R)-HNK, significantly improved the increased plasma levels of RANKL and decreased OPG/RANKL ratio in CSDS susceptible mice. Moreover, (R)-ketamine, but not (2R,6R)-HNK, significantly attenuated the decreased BMD in CSDS susceptible mice. These findings demonstrate that (R)-ketamine may have beneficial effects in depression-like phenotype and abnormalities in bone functions of CSDS susceptible mice. It is, therefore, likely that (R)-ketamine would be a potential therapeutic drug for abnormalities in bone metabolism in depressed patients.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
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- Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites Translational Psychiatry November 7, 2019
- A historical review of antidepressant effects of ketamine and its enantiomers. Pharmacology, Biochemistry, and Behavior February 5, 2020
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Cites 27
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
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