GLUCOCORTICOID NEGATIVE FEEDBACK ON THE HPA AXIS IN 5 INBRED RAT STRAINS

The aim of the present work was to study the influence of altering glu cocorticoid negative feedback on both basal activity of the hypothalam ic-pituitary-adrenal (HPA) axis and its response to acute stress (tail shock) in five inbred rat strains known to differ in some depression- like behaviors: Brown Norway (BN), Fischer 344 (F3441, Lewis new), spo ntaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats. Two comple mentary approaches were used: 1) enhancement of negative feedback by a dministration of 0.05 and 0.2 mg/kg dexamethasone (Dex) and 2) attentu ation of negative feedback by pharmacological adrenalectomy (PhADX). T he results indicate that 1) Lew rats consistently show adrenocorticotr opic hormone (ACTH) and corticosterone hyporesponsiveness to stress, 2 ) interstrain differences in the effect of Dex on the HPA axis were ve ry weak and not related apparently to differences in the metabolism of the steroid, 3) the suppressive effect of the highest dose of Dex on basal corticosterone levels was lower in BN rats than in the other str ains, and 4) after PhADX, an increase in ACTH levels was observed in r esponse to acute stress in BN, F344, and WKY but not in Lew and SHR ra ts, suggesting possible interstrain differences in pituitary sensitivi ty to neural stimuli induced by stress. In summary, our results indica te that there are differences among the strains with regard to both 2) the suppressive effect of Dex on the HPA axis, BN rats showing a cert ain degree of resistance, and 2) the capability of PhADX rats to respo nd to acute stress, which suggests a defective release of ACTH in Lew and SHR rats. The biological meaning of these alterations of corticost eroid negative feedback among the five inbred strains studied remains to be established.