Age-Dependent Effects of Chronic Stress on ACTH and Corticosterone Responses to an Acute Novel Stress

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Abstract
Aging effects on the hypothalamic-pituitary-adrenocortical system have been studied primarily in the sedentary, environmentally deprived laboratory rat. Since it is known that chronic activation changes the responsiveness of the hypothalamic-pituitary-adrenocortical system, the present experiments were undertaken to determine whether age-related effects on this system would differ between sedentary and chronically stressed rats. Groups of 6- and 20-month-old F-344 rats were exposed to daily sessions of a 2-way shock-escape procedure over a 6-month period. When the rats were 12 (adult) and 26 months of age (old), pituitary-adrenocortical responses to an acute, novel stimulus were examined in young and old chronically stressed and age-matched control rats. Young and old control rats showed essentially the same corticosterone response to an acute motion stress. Chronic stress exposure increased the corticosterone response to the novel acute stressor in young but not in old rats. ACTH levels in response to acute stress were significantly reduced in old control rats compared to young control animals. Chronic stress did not change in ACTH acute stress response in young animals, whereas in old animals chronic stress elevated the ACTH responsiveness so that the old rats showed stress-induced ACTH levels that were comparable to the young animals. In conclusion, the effects of chronic stress on the function of the hypothalamic-pituitary-adrenocortical system are age-dependent, and environmental factors can significantly influence the progression of aging of the hypothalamic-pituitary-adrenal system.