Ketamine’s Effects on the Glutamatergic and GABAergic Systems: A Proteomics and Metabolomics Study in Mice

Ketamine, a noncompetitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect and is used for patients experiencing treatment-resistant depression. We carried out a time-dependent targeted mass spectrometry-based metabolomics profiling analysis combined with a quantitative based on in vivo <sup>15</sup>N metabolic labeling proteome comparison of ketamine- and vehicle-treated mice. The metabolomics and proteomics datasets were used to further elucidate ketamine’s mode of action on the gamma-aminobutyric acid (GABA)ergic and glutamatergic systems. In addition, myelin basic protein levels were analyzed by Wester…