Individual differences in chronically defeated male mice: Behavioral, endocrine, immune, and neurotrophic changes as markers of vulnerability to the effects of stress

This study aimed to analyze different behavioral profiles in response to chronic social defeat using the sensorial contact model. We hypothesized that a passive profile, unlike an active one, would be associated with behavioral and physiological characteristics related to depression. Six-week-old OF1 male mice were subjected to defeat for 21 consecutive days. A combination of cluster and discriminant analyses of the behavior exhibited during confrontation on Day 21 established two behavioral profiles: active (n = 22) and passive (n = 34). Passive mice, with a high level of immobility and low non-social exploration, had higher plasma corticosterone concentrations than active mice after 21 days of defeat. Three days after the last defeat, passive mice had lower corticosterone levels than manipulated-control mice (n = 11). Higher levels of interleukin-6 and tumor necrosis factor-alpha (TNF-alpha) in the spleen and lower hippocampal brain-derived neurotrophic factor levels were observed in passive mice in comparison with those in active mice and the manipulated controls. The only differences observed in active mice in relation to the manipulated control were higher plasma corticosterone (Day 21) and TNF-alpha levels. The results show that different behavioral profiles in response to chronic defeat are associated with different physiological profiles, and that the passive profile presents physiological characteristics previously associated with depression.