Deciphering the Metabolome under Stress: Insights from Rodent Models

Despite intensive research efforts to understand the molecular underpinnings of psychological stress and stress responses, the underlying molecular mechanisms remain largely elusive. Towards this direction, a plethora of stress rodent models have been established to investigate the effects of exposure to different stressors. To decipher affected molecular pathways in a holistic manner in these models, metabolomics approaches addressing altered, small molecule signatures upon stress exposure in a high-throughput, quantitative manner provide insightful information on stress-induced systemic changes in the brain. In this review, we discuss stress models in mice and rats, followed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) metabolomics studies. We particularly focus on acute, chronic and early life stress paradigms, highlight how stress is assessed at the behavioral and molecular levels and focus on metabolomic outcomes in the brain and peripheral material such as plasma and serum. We then comment on common metabolomics patterns across different stress models and underline the need for unbiased -omics methodologies and follow-up studies of metabolomics outcomes to disentangle the complex pathobiology of stress and pertinent psychopathologies.