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

Stressors produce rapid activation of the hypothalamic-pituitary-adrenal axis, which typically resolves within 60-90 min following termination of the stressor. In addition, some stressors such as inescapable tailshock (IS) also produce elevated basal levels of corticosterone (CORT), and reduced serum levels of corticosteroid binding globulin (CBG). The elevated basal levels of CORT produced by IS are only observed at the trough of the circadian rhythm of CORT secretion, and are sustained for 2-3 days following stressor termination. The goal of the following experiments was to determine the extent to which the elevated basal levels of CORT observed following IS exposure produced greater corticosteroid receptor occupancy in the brain and pituitary. To do so, rats (n = 8-10 per group) received either sham or bilateral 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 mA, 5 s each) administered on a 60 s variable intertrial interval, or remained in their home cages. As seen previously, IS produced an increase in basal CORT (5 mu g/dl) and a decrease in CBG (30% decrease). Rats were sacrificed 24 h following IS for trunk blood samples and brain dissections. IS exposure had very little effect on corticosteroid receptor protein expression as 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 hypothalamus and posterior cortex. These long-term changes in corticosteroid receptor activation, evident 24 h after IS exposure, may be responsible for some of the long-term neural, behavioral and immune changes observed following this acute stress procedure. (C) 1999 Published by Elsevier Science B.V. All rights reserved.