Metabolite signature associated with stress susceptibility in socially defeated mice

Objective: Social defeat represents a naturalistic form of conditioned fear and is often used as an animal model of depression. The present study aimed to identify the neurochemicals in select brain regions of mice exposed to social defeat stress. Methods: Adult C57BL/6N mice were subjected social defeat stress for 10 days. Using high-resolution magic angle spinning ¹ H nuclear magnetic resonance (HR-MAS ¹ H NMR), untargeted metabolomes were measured in the amygdala (AMY), dorsal hippocampus (dHIP), dorsal striatum (dST), and prefrontal cortex (PFC). Results: We observed perturbations of glutamine in the AMY; glutamate in the dHIP; glycine and myo-inositol in the dST; and aspartate, choline, and phosphoethanolamine in the PFC of susceptible and/or unsusceptible groups compared to the control group. The susceptible and unsusceptible groups significantly differed with regard to three metabolites: glutamine, glycine, and choline. Conclusion: These findings suggest that social defeat stress induces disturbances in the metabolism of amino acids, lipids, and neurotransmitters in several brain areas. The resulting susceptibility-related metabolites may provide new insights into the pathophysiology underlying stress-related mental illness.