Influence of aging on chronic unpredictable mild stress-induced depression-like behavior in male C57BL/6J mice

•Male C57BL/6J mice exhibited depression-like behaviors induced by 3–8 weeks CUMS.•CUMS altered BDNF, Htr1a, and IL-6 expression in hippocampus.•The depressoin-like behavioral phenotype after CUMS were altered by increased age. Depression is a common psychiatric disorder that can occur throughout an individual’s lifespan. Chronic unpredictable mild stress (CUMS) protocol is currently the most commonly used to develop an animal model of depression. Due to the variable duration and procedure of CUMS, it is difficult to reproduce and explore the mechanism of CUMS-induced depression effectively. In the present study, the CUMS-induced behavioral phenotypes were assessed in male C57BL/6J mice at the age of 9–18 weeks. The mice stressed for 3–8 weeks exhibited lower body weight as well as longer immobility time of forced swim and tail suspension test compared to control mice. Moreover, lessening and impairment of hippocampal neurons was found in stressed mice at the age of 18 weeks, which was correlated with increased relative mRNA expression levels of inflammatory cytokines BDNF, Htr1a, and IL-6 in the hippocampus. Nevertheless, no difference between stressed and control mice was observed neither in the sucrose preference nor in the open field test (except for vertical activity in OFT) at the age of 18 weeks. These findings reveal that 3–8 weeks of chronic stress could induce depression-like alterations in male C57BL/6J mice and the behavioral adaptation of aged mice might fail to the availability of the depression model.