期刊
BEHAVIOURAL BRAIN RESEARCH
卷 368, 期 -, 页码 176-182出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2019.111904
关键词
(R)-ketamine; (2R,6R)-HNK; Inflammation; Bone; RANKL
资金
- China Scholarship Council, China
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 KB ligand (RANKL), and osteopontin after behavioral tests. (R)-ketamine, but not (2R,6R)-HNK, elicited rapid and sustained anti-depressant 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.
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