Multimodal MR identifies the prefrontal cortex as central hub of stress-induced brain alterations in rats

Motivation: Chronic unpredictable mild stress (CUMS) is utilized to model depression-like symptoms in rodents. Although the prevalence of depression is twice as high in women, 97% of CUMS studies focused on male animals. Goal(s): We aimed to comprehensively phenotype the effect of CUMS in female rats using MRI. Approach: Thus, we assessed a CUMS-induced depression-like phenotype with various behavioral tests and multimodal MRI specifically in females. Results: We found prominent prefrontal and striatal volume loss, together with prefrontal glutamate reduction, and decreased top-down prefrontal control of the nucleus accumbens, corroborating the high sensibility of the PFC to chronic stress in the female population. Impact: We identified the prefrontal cortex as the central hub of chronic stress-induced changes in brain function in a female population of animals using multimodal MRI, thus creating a model for further investigation of distinct effects in possible treatments.