Role of Inflammatory Bone Markers in the Antidepressant Actions of ( R)-Ketamine in a Chronic Social Defeat Stress Model

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.