Social stress induces glucocorticoid resistance in subordinate animals

Introducing an aggressive intruder into a cage of mice (social disruption, SDR) resulted in intense fighting and defeat of the cage residents. Defeat was accompanied by elevated levels of serum corticosterone and nerve growth factor (NGF). Repeated exposure to an intruder induced a state of glucocorticoid resistance in peripheral immune cells. The present study sought to examine the behavioral factors that mediated the development of glucocorticoid resistance following SDR. Glucocorticoid resistance developed in animals that exhibited a subordinate behavioral profile, which consisted of a low tendency for social investigation and a high level of submissive behavior in response to the intruder's attacks. Glucocorticoid resistance was also linked to the presence of injuries due to fighting, but not to changes in systemic levels of either corticosterone or NGF. Since a submissive behavioral profile is associated with increased risk for injuries due to fighting, it may be that the development of glucocorticoid resistance is an adaptive mechanism that allows the inflammatory component of wound healing to occur in the presence of high levels of corticosterone. Together, these findings demonstrate that the outcomes of social stress may be modified by physiological changes associated with wounding, as well as by behavioral variables such as social status.