Long-term changes in mineralocorticoid and glucocorticoid receptor occupancy following exposure to an acute stressor

Stressors produce rapid activation of the hypothalamic-pituitary-adrenal ax is, which typically resolves within 60-90 min following termination of the stressor. In addition, some stressors such as inescapable tailshock (IS) al so produce elevated basal levels of corticosterone (CORT), and reduced seru m levels of corticosteroid binding globulin (CBG). The elevated basal level s of CORT produced by IS are only observed at the trough of the circadian r hythm of CORT secretion, and are sustained for 2-3 days following stressor termination. The goal of the following experiments was to determine the ext ent to which the elevated basal levels of CORT observed following IS exposu re produced greater corticosteroid receptor occupancy in the brain and pitu itary. To do so, rats (n = 8-10 per group) received either sham or bilatera l adrenalectomy (with CORT replacement in their drinking water; 25 mu g/ml) and were given 3 days to recover. Rats were then exposed to 100 ISs (1.6 m A, 5 s each) administered on a 60 s variable intertrial interval, or remain ed in their home cages. As seen previously, IS produced an increase in basa l CORT (5 mu g/dl) and a decrease in CBG (30% decrease). Rats were sacrific ed 24 h following IS for trunk blood samples and brain dissections. IS expo sure had very little effect on corticosteroid receptor protein expression a s determined by mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) binding levels in ADX rats. In addition, no changes in whole cell GR levels (as detected by Western blot) were observed in sham rats exposed to IS. On the other hand, IS exposure led to greater occupancy of MR (ranging from 25%-50%) in hippocampus, hypothalamus, pituitary, and posterior cortex . IS also produced greater occupancy of GR (approximately 20%) in hypothala mus and posterior cortex. These long-term changes in corticosteroid recepto r activation, evident 24 h after IS exposure, may be responsible for some o f the long-term neural, behavioral and immune changes observed following th is acute stress procedure. (C) 1999 Published by Elsevier Science B.V. All rights reserved.