osteoprotegerin and Depressive-Disorder

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.

Topics: Animals; Antidepressive Agents; Biomarkers; Bone Density; Depression; Depressive Disorder; Disease Models, Animal; Inflammation; Ketamine; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Osteopontin; Osteoprotegerin; RANK Ligand; Stress, Psychological

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.. 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.. (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.. Our findings demonstrate that inflammatory bone markers may play a role in the antidepressant effects of (R)-ketamine.

Topics: Animals; Antidepressive Agents; Biomarkers; Depressive Disorder; Disease Models, Animal; Dominance-Subordination; Ketamine; Male; Mice, Inbred C57BL; Osteopontin; Osteoprotegerin; Random Allocation; RANK Ligand; Stress, Psychological