Conclusions
Our findings suggest that skeletal muscular glycine contributes to the antidepressant effects of ketamine in inflammation. Effective strategies for improving skeletal muscular glycine levels may be a novel approach to depression treatment.
Methods
Non-targeted metabolomics, western blotting, and behavioral tests (locomotion, tail suspension, and forced swimming tests) were performed. Result: Ketamine significantly attenuated the abnormally increased immobility time in a lipopolysaccharide (LPS)-induced mouse model of depression. Aminomalonic acid, glutaraldehyde, glycine, histidine, N-methyl-L-glutamic acid, and ribose levels in skeletal muscle were altered following ketamine administration. Furthermore, ketamine significantly decreased the LPS-induced increase in glycine receptor A1 (GlyA1) levels. However, the glycine receptor antagonist strychnine did not elicit any pharmacological effects on ketamine-induced alterations in behaviors or muscular GlyA1 levels. Exogenous glycine and L-serine significantly improved depression-like symptoms in LPS-induced mice. Conclusions: Our findings suggest that skeletal muscular glycine contributes to the antidepressant effects of ketamine in inflammation. Effective strategies for improving skeletal muscular glycine levels may be a novel approach to depression treatment.