Decreased sensitivity to glucocorticoid fast feedback in chronically stressed rats.

A number of changes in anterior pituitary corticotrophs occur after chronic footshock. These include increased ACTH and beta-endorphin content and a loss of glucocorticoid negative feedback on corticotropin-releasing hormone (CRH)-stimulated ACTH and beta-endorphin secretion, without changes in sensitivity to ovine CRH examined in vitro. The present studies were undertaken to determine whether the in vitro changes were reflected by similar changes in vivo. We developed a fast feedback paradigm using a 5-min swim stress as challenge, with injection of saline or corticosterone immediately prior to swim. Corticosterone reliably decreased ACTH and beta-endorphin responses to swim over the 30-min period studied. This feedback inhibition did not occur in rats that were either exposed to 30 min of chronic footshock for 7 or 14 days or in rats that were treated with corticosterone daily for 14 days in a regimen that has been reported to decrease hippocampal glucocorticoid receptors. By contrast, in rats exposed to the less intense stimulus of 30 min swim for 14 days, the fast feedback action of corticosterone was intact. These results suggest that both fast and delayed feedback corticosterone-inhibitory mechanisms may be blocked by relatively high levels of chronic stress or by chronic treatment with corticosterone, possibly as a consequence of decreased hippocampal glucocorticoid receptor number.