Previous exposure to immobilisation and repeated exposure to a novel environment demonstrate a marked dissociation between behavioral and pituitary-adrenal responses.

Activation of the hypothalamus-pituitary-adrenal (HPA) axis is presumably related to the degree of novelty and considered to reflect emotional reactivity. Exposure to novel environments can allow us to simultaneously evaluate both behavior and HPA activation and therefore it is an appropriate design to directly study the relationship between both responses. In the present experiment, we studied how previous exposure to a severe stressor (2 h of immobilisation, IMO, 5 days before testing) and repeated exposure to the same novel environment (a holeboard, HB) altered behavioral and HPA response to the HB. Previous exposure to IMO did not alter any behavior during the first exposure to the HB (5 min), but elicited a greater ACTH response as compared to stress-naive rats. However, corticosterone response did not differ between groups, probably because maximum corticosterone levels are never reached before 15-20 min. Repeated exposure of IMO and stress-naive rats to the HB every other day resulted in progressively lower levels of activity/exploration in both groups, whereas the ACTH and corticosterone responses were basically maintained intact over the days. The present results demonstrate a double dissociation between behavior and HPA activation in the HB. First, a single exposure to IMO elicited a long-lasting sensitisation of the HPA axis that apparently was not a direct consequence of fear/anxiety elicited by the novel environment. Second, progressive familiarisation of the animals with a novel environment resulting in apparently lower levels of motivation to explore did not appear to reduce the stressful properties of the situation as evaluated by ACTH release.