HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSE TO CHRONIC STRESS IN 5 INBREDRAT STRAINS - DIFFERENTIAL RESPONSES ARE MAINLY LOCATED AT THE ADRENOCORTICAL LEVEL

The effects of chronic stress on the hypothalamic-pituitary-adrenocort ical (HPA) axis were studied in five inbred rat strains, i.e. Brown No rway (BN), Fischer (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR ) and Wistar Kyoto (WKY). Previously, these rat strains had been shown to display clear behavioral differences in the forced swimming test t hat presumably measures depression-like behavior, BN and WKY being mor e passive than the other strains. Here we test the hypothesis that the differences in behavioral immobility might be associated with an abno rmal HPA response to chronic immobilization (IMO) stress. In stress-na ive rats under basal conditions (morning) there were no differences am ong strains in adrenal weight, serum adrenocorticotropin hormone (ACTH ) and corticosterone (B) levels, corticotropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and hippocampal glucocorticoid and mineralocorticoid receptor (GR and MR) mRNA. After chronic IMO, basal serum ACTH levels were increased in LEW, SHR and W KY, but not in BN or FIS rats, whereas basal B levels were increased i n BN, FIS, SHR and WKY rats, but not in LEW. The increase in adrenal w eight was also strain dependent and correlated negatively with chronic IMO-induced hypercorticosteronemia. These peripheral differences amon g strains were not observed at central levels. Thus, chronic IMO incre ased the CRF mRNA content in the PVN, analyzed by in situ hybridizatio n, similarly in all strains. In addition, after chronic IMO no differe nces were found among strains in hippocampal GR mRNA and RM mRNA conte nts. Considering data from all strains together, chronic IMO reduced t he GR mRNA (50-60%) content in the hippocampal CA1, CA3 and DG areas, and slightly diminished (11-13%) MR mRNA levels in CA1 and CA3 areas. The present results indicate that: (i) chronic IMO down-regulates GR m RNA in the hippocampus and slightly up-regulates CRF mRNA in the hypot halamic PVN similarly in all strains; (ii) after chronic IMO interstra in differences were observed in serum ACTH and B levels as well as adr enal hypertrophy; (iii) some changes are probably located at the adren al level since changes in serum B level and adrenal weight were not re lated to changes in ACTH; (iv) in LEW and WKY rats, B hyporesponsivene ss to chronic IMO might be linked to low adrenal sensitivity to ACTH, and (v) HPA axis changes induced by the chronic IMO procedure are not related to previously reported data on depressive-like behavior of BN and WKY in the forced swimming test.