title: Corticosterone modulates autonomic responses and adaptation of central immediate-early gene expression to repeated restraint stress.
abstract: We have tested the role of elevated corticosterone in modulating the responses to either a single (acute) or chronic (repeated daily) restraint stress. Male rats were adrenalectomised, and received subcutaneous corticosterone pellets that resulted in either low (ca. 60 ng/ml) or higher (ca. 130-150 ng/ml) levels of plasma corticosterone. They were also implanted with telemetric transmitters relaying heart rate and core temperature. Control rats were unoperated and untreated. In the first experiment, rats were exposed to daily (60 min) restraint stress for 9 days whereas in the second experiments, rats were only exposed to a single restraint stress. Heart rate and core temperature were recorded every 10 min during each stress session. Brains were removed 1 h after the end of the final stress, and stained immunocytochemically for Fos, Fos-b. Plasma corticosterone was measured by radioimmunoassay. Control rats showed marked tachycardia, peaking at about 10 min and declining thereafter (habituation). This pattern did not change significantly across the 9 days of repeated stress. Rats with low dose corticosterone replacement showed a different pattern: maximal heart rate responses were similar, but elevated heart rate persisted during the period of stress. This effect was most marked on the first exposure to restraint. In contrast, high dose replacement rats showed similar heart rate responses to controls. Restraint stress induced a transient hypothermia, which in control rats was reduced during repeated stress (adaptation). High dose corticosterone resulted in accelerated adaptation of this response. As expected, an acute stress increased Fos expression in a range of limbic structures including the lateral septum, lateral preoptic area, bed nucleus of the stria terminalis, and three divisions of the hypothalamic paraventricular nucleus and in the raphe, locus coeruleus and solitary nucleus of the brainstem. After 9 days, there was no longer increased Fos expression in any of these areas. There was no effect of corticosterone treatment on Fos expression after an acute stress, and following repeated stress the low dose group showed increased expression in the lateral preoptic area only. Results with Fos-b were quite different. The effects of an acute stress in control animals was similar to that observed for Fos. Corticosterone had no effects on Fos-b expression after a single stress. Following repeated stress, there were still elevations of Fos-b (compared to controls) in the lateral septum, and in the basolateral and medial amygdala. Rats receiving low dose corticosterone showed increased Fos-b expression following 9 days stress in the lateral septum and in the dorsal and medial parts of the paraventricular nucleus compared to either control, stressed rats or those receiving the higher corticosterone dose and repeated stress. From these results we suggest that persistently elevated corticosterone acts to reduce ('shut-off') stress-induced responses as assessed both by the reaction of the autonomic system and by the expression of immediate-early genes in the brain. However, there are marked differences in the relations between corticosterone and the parameters measured in our experiments. In particular, there are distinctions between Fos and Fos-b both in the way they adapt to repeated restraint stress, and the effect corticosterone has on this adaptive process.
authors.affiliation: Anatomy Department, University of Cambridge, Downing Street, CB2 3DY, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Stamp
authors.forename: J
authors.initials: J
authors.lastname: Herbert
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D004435:Eating; D015870:Gene Expression / Q000502:physiology*; D017781:Genes, Immediate-Early; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D013686:Telemetry; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D003345:Corticosterone