DIRECT EVIDENCE FOR CHRONIC STRESS-INDUCED FACILITATION OF THE ADRENOCORTICOTROPIN RESPONSE TO A NOVEL ACUTE STRESSOR

The ACTH response to CRF and the role of glucocorticoids on the pituit ary-adrenal responsiveness to acute stressors after a period of chroni c stress were assessed in Sprague-Dawley rats. After chronic immobiliz ation (IMO) an enhanced ACTH response to CRF administration was observ ed. In another experiment, control and chronic IMO rats were adrenalec tomized (ADX) or sham-adrenalectomized (SHAM) and 2 days later killed in resting conditions or after having been subjected to acute IMO or t ail-shock for 30 min. Chronic IMO increased basal corticosterone but n ot adrenocorticotropin (ACTH) levels in SHAM rats. As expected, ADX in creased ACTH levels in all conditions. In response to the novel acute stressor (shock), ACTH levels were drastically dependent on the presen ce of corticosterone: thus, whereas in SHAM rats chronic IMO reduced t he ACTH response to shock, in ADX rats a clear enhancement of the ACTH response to shock was observed in chronic IMO rats. In order to demon strate that, in our experimental conditions, chronic stress also induc es down-regulation of glucocorticoid receptors in the hippocampus, an additional experiment was done: rats subjected chronically to IMO or a dministered 5 mg corticosterone (B) were adrenalectomized and killed 2 0 h later under basal conditions. Both chronic IMO and chronic B admin istration decreased glucocorticoid type II binding in the hippocampus. From these results, it is concluded that chronic IMO induces facilita tion of the ACTH response to novel acute stressors which is uncovered after corticosterone removal.