Superimposed cold stress-induced hypothalamic-pituitary-adrenal response during long-duration restraint stress.

It has been reported that animals exposed to prior stress exhibit enhanced, reduced or equivalent hypothalamic-pituitary-adrenal (HPA) response to a subsequent acute stressor. We demonstrated previously that a long-duration restraint stress (RTS) evoked adaptive change, characterized by transient increase and gradual recovery to basal level in c-fos mRNA/c-fos protein (Fos) expression in the hypothalamic paraventricular nucleus (PVN) and in plasma adrenocorticotropin (ACTH) levels, although circulating corticosterone (CORT) remained at a high level. In order to investigate the HPA response to another stressor during the adaptive phase of long-duration RTS, we superimposed acute cold stressor (CS) to 16 hours RTS rats. Superimposed CS-induced re-expression of c-fos mRNA/Fos in the parvocellular region of the PVN (PVNpv) was observed in 16 hours RTS rats. The degree of expression of c-fos gene in superimposed CS rats was the same as those observed in single CS rats. The plasma ACTH levels induced by superimposed CS in 16 hours RTS rats were significantly higher compared with those in single CS rats. On the other hand, there were no significant differences between plasma CORT levels induced by superimposed CS in 16 hours RTS rats and those in single CS rats, and between plasma CORT levels before and after additional CS exposure in 16 hours RTS rats. The present study indicated that c-fos gene expression in PVN induced by superimposed CS was normo-responsive, ACTH secretion was hyper-responsive (facilitation), CORT secretion was slightly increased, but not hyper-responsive in long-duration RTS rats. These findings suggest that stress response induced by superimposed CS during long-duration RTS may occur in a different way at each level of the HPA.