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.
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