Dataset Information

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 ?B 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 ?B ligand in chronic social defeat stress-susceptible mice. We found a positive correlation between sucrose preference and osteoprotegerin/receptor activator of nuclear factor ?B ligand ratio. Conclusions:Our findings demonstrate that inflammatory bone markers may play a role in the antidepressant effects of (R)-ketamine.

SUBMITTER: Zhang K

PROVIDER: S-EPMC6209851 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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

Zhang Kai K Ma Min M Dong Chao C Hashimoto Kenji K

The international journal of neuropsychopharmacology 20181101 11

<h4>Background</h4>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.<h4>Methods</h4>Behavioral tests for antidepressant actions were performed after a single administration of (R)-ketamine or (S)-ketamine. We measured infl ...[more]

PMID: 30032169

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Project description:SKF83959 stimulates the phospholipase Cβ/inositol phosphate 3 pathway, resulting in the activation of Ca(2+)/calmodulin-dependent kinase IIα, which affects the synthesis of brain-derived neurotrophic factor, a neurotrophic factor critical for the pathophysiology of depression. Previous reports showed that SKF83959 elicited antidepressant activity in the forced swim test and tail suspension test as a novel triple reuptake inhibitor. However, there are no studies showing the effects of SKF83959 in a chronic stress model of depression and the role of phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway in SKF83959-mediated antidepressant effects. In this study, SKF83959 was firstly investigated in the chronic social defeat stress model of depression. The changes in hippocampal neurogenesis, dendrite spine density, and brain-derived neurotrophic factor signaling pathway after chronic social defeat stress and SKF83959 treatment were then investigated. Pharmacological inhibitors and small interfering RNA/short hairpin RNA methods were further used to explore the antidepressive mechanisms of SKF83959. We found that SKF83959 produced antidepressant effects in the chronic social defeat stress model and also restored the chronic social defeat stress-induced decrease in hippocampal brain-derived neurotrophic factor signaling pathway, dendritic spine density, and neurogenesis. By using various inhibitors and siRNA/shRNA methods, we further demonstrated that the hippocampal dopamine D5 receptor, phospholipase C/inositol phosphate 3/ calmodulin-dependent kinase IIα pathway, and brain-derived neurotrophic factor system are all necessary for the SKF83959 effects. These results suggest that SKF83959 can be developed as a novel antidepressant and produces antidepressant effects via the hippocampal D5/ phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway.

Dataset Information

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

Publications

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

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