Persistent stress-induced elevations of urinary corticosterone in rats.

Exposure of rats to inescapable stressors (IS) results in persistent elevations in plasma corticosterone (CORT), which are selective to the trough of the circadian rhythm. Although affective disorders (depression, anxiety) in humans are also characterized by persistent hypothalamic-pituitary-adrenal axis (HPAA) activation, the predominant measure of HPAA activation in clinical studies is 24-h urinary cortisol. To facilitate interspecies comparisons regarding the persistent effects of stress on HPAA activity, we compared the effects of IS on plasma and urinary CORT in rats. Male Sprague-Dawley rats were exposed to three 2-h sessions of IS (40, 2.0 mA tailshocks) or remained in their home cages. The 24-h urine samples were collected daily from 2 days prior to stress to 5 days after stressor cessation, then weekly for 3 weeks. In addition, plasma samples were obtained at 08:00 (trough) and 20:00 hours (peak) for the first 3 days after stressor cessation and weekly for 3 weeks thereafter. Consistent with our earlier work, plasma CORT elevations were apparent in the trough, but not the peak samples for 3 days after stressor cessation. The 24-h urinary CORT levels were elevated during stressor exposure, and remained elevated for 3 days after stressor cessation. Persistent stress-induced urinary CORT elevations in rats are reminiscent of the clinical HPAA abnormalities described for major depression and affective disorders.