Depression is a severe and chronic

Depression is a severe and chronic mental disorder, affecting about 322 million individuals worldwide. A recent studyshowed that diterpene ginkgolides (DG) have antidepressant-like effects on baseline behaviours in mice. Here, weexamined the effects of DG and venlafaxine (VLX) in a chronic social defeat stress model of depression. Both DG andVLX attenuated stress-induced social deficits, despair behaviour and exploratory behaviour. To elucidate themetabolic changes underlying the antidepressive effects of DG and VLX, we investigated candidate functionalpathways in the prefrontal cortex using a GC-MS-based metabolomics approach. Metabolic functions and pathwaysanalysis revealed that DG and VLX affect protein biosynthesis and nucleotide metabolism to enhance cell proliferation,with DG having a weaker impact than VLX. Glutamate and aspartate metabolism played important roles in theantidepressant effects of DG and VLX. Tyrosine degradation and cell-to-cell signaling and interaction helpeddiscriminate the two antidepressants. L-glutamic acid was negatively correlated, while hypoxanthine was positivelycorrelated, with the social interaction ratio. Understanding the metabolic changes produced by DG and VLX shouldprovide insight into the mechanisms of action of these drugs and aid in the development of novel therapies fordepression.