title: Hypothalamic-pituitary-adrenal function in chronic intermittently cold-stressed neonatally handled and non handled rats.
abstract: Neonatally handled (H) animals, as adults, exhibit lower ACTH and corticosterone (B) responses to a number of acute stressors compared to their non-handled (NH) counterparts. However, little is known about activity within the hypothalamic-pituitary-adrenal (HPA) axis of H and NH animals under conditions of chronic stress. We, therefore, examined HPA function in adult H and NH rats exposed to chronic intermittent cold stress (4 h of 4 degrees C cold a day for 21 days; H CHR and NH CHR) and in control H and NH (H CTL and NH CTL) rats. H CTL and NH CTL animals displayed comparable ACTH and B responses to a single, acute exposure to cold. We found that H CHR animals exhibited lower levels of ACTH, but not B, during the 21st exposure to cold (the homotypic stressor) compared to the first exposure to cold in H CTL; however, ACTH and B levels in NH CHR were not different from those in NH CTL. In contrast, NH CHR animals hypersecreted ACTH and B in response to restraint (the novel, heterotypic stressor) compared to NH CTL and both H groups, whereas H CHR and H CTL animals did not differ in their responses to restraint. These endocrine responses were associated with increased basal median eminence levels of both CRH and AVP in H CHR and NH CHR relative to their control groups (with NH CHR exhibiting the highest absolute levels of each secretagogue), and with decreased glucocorticoid receptor densities in septum of both H CHR and NH CHR. In addition, the expected lower glucocorticoid receptor density in hippocampus and frontal cortex of NH rats compared to H rats was observed. We believe that the difference in glucocorticoid receptor density between H and NH animals in the hippocampus and frontal cortex and the associated differences in secretagogue content in the median eminence are related to the hypersecretion of ACTH and B in the NH CHR relative to the other groups. Furthermore, we hypothesize that an active inhibitory process is involved in the adaptation of HPA responses of H CHR animals to the homotypic stressor, and present a working model of regulation of activity within the CRH/AVP neurons in the PVN.
authors.affiliation: Douglas Hospital Research Center, Department of Neurology & Neurosurgery, McGill University, Montreal, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Bhatnagar
authors.forename: M J
authors.initials: MJ
authors.lastname: Meaney
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001481:Basal Metabolism; D002908:Chronic Disease; D003080:Cold Temperature; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D006234:Handling, Psychological; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology*
chemical_list: D001127:Arginine Vasopressin; D010121:Oxytocin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone