Recovery of the Hypothalamic-Pituitary-Adrenal Response to Stress

Abstract

Pathological consequences of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may be related to the duration rather than to the intensity of HPA axis activation after exposure to the stressor. Consequently a fine analysis of post-stress events is of importance. The present experiments were designed to study the importance of three key factors in HPA recovery: intensity of the stressor (experiment 1), duration of exposure to the stressor (experiment 2) and previous experience of the animals with the situation (experiments 3 and 4). In experiment 1, analysis of both the response to the stressor and the poststress period showed that the stronger the stressor, the greater the area under the curve of HPA activation. In experiment 2, different groups of rats were exposed to different periods of immobilization (IMO) (20 min, 1 h and 2 h) and sampled before, during and after exposure to IMO. The speed of recovery of plasma corticotropin (ACTH) levels was not related to the duration of exposure to the stressor. In experiments 3 and 4, the influence of previous experience with the stressor was studied in rats daily exposed to 20 min IMO or daily injected with hypertonic saline (HS) for 8 days and sampled on days 1, 2, 5 and 8. Whereas a significant decline in plasma ACTH levels was not observed immediately after IMO until day 8, a single previous exposure to IMO was enough to enhance recovery 90 min after the end of exposure to IMO. Corticosterone levels were related to the number of previous experiences with the stressor only in the post-IMO period. In response to a novel stressor (forced swimming), chronic IMO rats showed a slightly impaired recovery as compared to stress-naive rats, suggesting that enhanced recovery of the HPA axis was specific for the homotypic stressor. After daily HS injections, a pattern similar to that after IMO was observed, the delayed, but not the early response of the HPA axis being reduced as a function of the number of previous experiences with the situation. Taken together, the present results suggest that the speed of recovery of the HPA axis after its activation by stressors is sensitive to the intensity of the stressors but not to their duration, and that adaptation to a repeated stressor is more apparent during the delayed HPA response.

Substance P in the medial amygdala: Emotional stress-sensitive release and modulation of anxiety-related behavior in rats

“…Immobilization is known to be a severe stressor accompanied by a pronounced ACTH (corticotropin) response (42). Our finding that comparatively mild emotional stress such as elevated platform exposure was sufficient to trigger the release of SP in the MeA contributes to a growing literature that SP functions as a stress neurotransmitter͞neuromodulator in the CNS.…”

Differential Effects of Rapid Eye Movement Sleep Deprivation and Immobilization Stress on Blood Lymphocyte Subsets in Rats

“…Nevertheless, chronic immobilization stress induces a decrease in ACTH elevation, measured immediately after the stress, and a faster return to basal levels. This faster return to basal levels is also displayed by corticosterone [30]. In addition, Bauer et al [31] report that after acute restraint stress, rats display a significant increase in plasma corticosterone and a suppression of peripheral blood lymphocyte proliferation.…”

Brain Glucocorticoid Receptor and Heat Shock Protein 70 Levels in Rats Exposed to Acute, Chronic or Combined Stress

“…In view of the new insights in the involvement of the hippocampus and brain cortex in the regulation of stress response [1][2][3][17][18][19] and the well established molecular mechanism by which glucocorticoids accomplish their function via glucocorticoid receptor (GR) and GR-associated proteins [5,[9][10][11][12][14][15][16], it was of interest to determine the changes in hippocampal and cortical GR and Hsp 70 after various stressors applied in the present study.…”

“…It has been shown that animals chronically exposed to a particular stressor display an exaggerated response of the limbic-hypothalamo-pituitary adrenal (LHPA) axis to various novel stressors, as judged by the plasma level of glucocorticoids and ACTH [17][18][19]. In addition to that, a number of data indicated that apart from the hippocampus, chronic stress may also affect the brain cortex [20][21][22].…”