Repeated stress persistently elevates morning, but not evening, plasma corticosterone levels in male rats

Repeated exposures to a stressor in our rat model of a chronic stress state cause elevated plasma corticosterone levels in the morning for several days after the last stressor. However, plasma corticosterone levels are normally characterized by a circadian rhythm with low levels for much of the morning and higher levels near the onset of darkness. The current experiment examined the question of whether the elevated morning levels after stressor exposures were accompanied by other changes in this circadian rhythm. Male rats were given restraint-shock stressor sessions for 0, 1, or 3 days, after which plasma samples were collected for 3 days at 0900 h and at three other times around the circadian peak (1400, 1800, and 2200 h). Plasma corticosterone levels at 0900 h were elevated for the first 2 days after three stressor exposures and for 1 day after a single stressor exposure compared to those in nonstressed controls. However, levels at 1400, 1800, and 2200 h were not different in stressed and control rats on the first 2 days after stressor exposures. In addition, the amplitude of the corticosterone rhythm was suppressed after three stressor exposures, but not after one. This decease in amplitude was mostly due to increased morning levels, inasmuch as the evening levels were similar in stressed rats and controls. Because the hypothalamic-pituitary-adrenal axis is more sensitive to glucocorticoid feedback in the morning, our data suggest that the mechanisms mediating feedback at this time of day may be disrupted by repeated stressor exposures. However, when feedback sensitivity is lower in the evening, repeated stressor exposures had little or no effect on plasma corticosterone levels.