Is repeated exposure to immobilization needed to induce adaptation of the hypothalamic-pituitary-adrenal axis? Influence of adrenal factors.

We have previously observed that a single exposure to a severe stressor such as immobilization in wooden boards (IMO) resulted in a faster return of plasma corticosterone (and to a lesser extent of ACTH) to basal activity when the rats were exposed again to the same stressor. In addition, the effect enhanced with time (days) elapsed between the two exposures. These data raised the question of to what extent adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated stress might be, at least partially, explained by the time elapsed between the two exposures rather than by daily repetition of the stressor. To answer this question and the role of glucocorticoids in the process, we studied the effects of single versus repeated exposure to IMO on the HPA response to the same stressor in both sham-operated and adrenalectomized rats maintained with corticosterone in their drinking saline (ADX+B). In sham rats, daily exposure to 20 min IMO for 9 days resulted in a decrease of the ACTH response to the stressor and a faster return of corticosterone to basal levels in the post-stress period. Similar effects were observed with a single session of IMO 8 days before. In ADX+B rats, a reduction of the ACTH response to the stressor was observed in repeated IMO rats but not in single IMO rats. The present results suggest that (i) in sham rats, a single exposure to IMO can induce a degree of adaptation of the HPA response to the same stressor applied days later that is very similar to that caused by repeated exposure to the situation; (ii) stress-induced release of glucocorticoids (or other adrenal factors) is not mandatory for the development of adaptation of the HPA axis to repeated stress, but may be involved in the long-term effects of a single exposure to stress.