Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats.

Repeated stress is an important risk factor for the development of depression. However, the mechanism by which stress influences depression is largely unknown, in part due to the fact that few animal models of repeated stress produce robust changes in depression-like behavior. The purpose of the present study was to characterize the effect of repeated corticosterone (CORT) injections and repeated restraint stress on anxiety and depression-like behavior in male rats. Rats received CORT injections (40 mg/kg, s.c.), vehicle injections, restraint stress (6 h/day), or handling once per day for 21 consecutive days prior to the behavioral testing. The rats were then tested for changes in fearful/anxious behavior in the open-field and social interaction tests and for depression-like behavior in the forced swim test. The repeated CORT injections had no significant effect on activity levels or anxiety in the open-field or social interaction tests. However, they did increase depression-like behaviors in the forced swim test. Repeated restraint stress had no significant effect on anxiety or depression-like behavior on any of the behavioral tests. These results suggest that repeated CORT injections warrant further investigation as an animal model to study the role of stress in depression.