Sex-Specific Social Effects on Depression-Related Behavioral Phenotypes in Mice

Social interaction and empathy play critical roles in determining the emotional well-being of humans. Stress-related depression and anxiety can be exacerbated or mitigated depending on specific social conditions. Although rodents are well known to exhibit emotional contagion and consolation behavior, the effects of group housing on stress-induced phenotypes in both males and females are not well established. Here, we investigated how the presence of stressed or unstressed conspecifics within a cage impact depression-related phenotypes. We housed male and female C57BL/6J mice in same-sex groups and subjected them to either gentle handling (GH) or the daily administration of corticosterone (CORT) for 10 days. The GH and CORT treatment groups were divided into cages of unmixed (GH or CORT) and mixed (GH and CORT) treatments. Depression-related phenotypes were measured using the forced swim test (FST) and sucrose preference test (SPT). We found that mixed housing alters FST behavior in a sex-specific manner. Male mice given chronic corticosterone (CORT) that were housed in the same cage as gently handled animals (GH) exhibited increased immobility, whereas GH females housed with CORT females demonstrated the opposite effect. This study underscores the importance of social housing conditions when evaluating stress-induced behavioral phenotypes and suggests that mixed cages of GH and CORT animals yield the greatest difference between treatment groups. The latter finding has important implications for identifying therapeutics capable of rescuing stress-induced behavioral deficits in the FST.