Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability

Depression is currently among the top five leading causes of the global burden of disease. Chronic unpredictable mild stress (CUMS) is currently the most commonly used, reliable, and effective rodent model of depression. However, for unclear reasons, this protocol is often difficult to reproduce in different laboratories. We performed a meta-analysis of studies that used the CUMS paradigm to evaluate depressive-like behavior in rodents. We sought to identify strain-dependent susceptibility to stress based on the development of one of the main end points of the model, anhedonia. The meta-analysis indicated that the CUMS protocol is a robust animal model of depression and is strongly associated with anhedonic behavior in rodents. However, high heterogeneity was found in the single subgroup analysis, which was attributable to modification of the CUMS and sucrose preference protocols. This may explain difficulties in reproducing stress protocols by different research groups.