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 glucocor ticoid resistance in peripheral immune cells. The present study sought to e xamine the behavioral factors that mediated the development of glucocortico id 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 i n response to the intruder's attacks. Glucocorticoid resistance was also li nked to the presence of injuries due to fighting, but not to changes in sys temic levels of either corticosterone or Nor. 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 me chanism that allows the inflammatory component of wound healing to occur in the presence of high levels of corticosterone. Together, these findings de monstrate that the outcomes of social stress may be modified by physiologic al changes associated with wounding, as well as by behavioral variables suc h as social status. (C) 2001 Academic Press.