Plasma Metabolomic Profiling of Repeated Restraint Stress in Rats

Exposure to repeated stress is associated with the occurrence and development of many prevalent diseases. Here, we evaluated the impact of a repeated restraint stress (RRS) paradigm on male Wistar rats and compared global plasma metabolites in stressed and unstressed rats using an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) approach and multivariate statistical analysis. The data showed that ten days of RRS induced weight loss and anxiety-like behavior, possibly through elevating plasma corticosterone levels in rats. Different metabolic characteristics were found between the two groups. Seventeen differential metabolites were identified and considered as potential biomarkers in the stress process, including histidine metabolism, neurotransmitter synthesis, and bile acid metabolism. Furthermore, l-carnosine, an identified metabolite, was examined in the same model and found to attenuate weight loss and anxiety-like behavior in RRS rats. Hence, these findings describe the metabolomic profiling of repeated stress and provide new insights into the pathophysiological mechanism of stress-induced deflections and potential pharmacological interventions.