Research reportA 1H-NMR plasma metabonomic study of acute and chronic stress models of depression in rats

To investigate and compare the metabonomic profiles of three stress-based models of depression, the effects of acute and chronic stress on the production of systemic endogenous metabolites were investigated. Such metabonomic analysis may provide researchers a new way of selecting appropriate animal models for the study of depression and antidepressants. Rats were subjected to one of three stress-based models: CUMS, FST-1d, or FST-14d. Endogenous metabolites excreted in plasma were analyzed using NMR in conjunction with multivariate and statistical techniques. The metabonomic study indicated that the concentration of different plasma metabolites could be used to differentiate among depression models: TMA, aspartic acid, glutamate, AcAc, NAc, alanine, lactate, Leu/Ile, lipids increased and proline, β-HB, valine decreased in the CUMS model; TMA decreased in the FST-1d model; α-glucose, β-glucose, β-HB, valine and lipids increased in the FST-14d model. The results suggested that metabonomics is a potentially appropriate method for evaluating depression models. According to the metabonomics study, CUMS model was more suitable and sensitive than the acute FST-1d model and predictable FST-14d model. The CUMS model was more appropriate for investigating both the efficacy of antidepressants and their mechanisms of action, while the FST-14d model should only be used for evaluating the efficacy of treatment.

96Highlights► Three depression models of CUMS, FST and FST-14d were investigated. ► Behavior research and 1H NMR metabonomics were used. ► CUMS model is more appropriate than FST or FST-14d for the mechanism study. ► FST-14 model can partly substitute the CUMS for the evaluation of antidepressant.