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      Effects of Chronic Social Stress on Neuroendocrine Responsiveness to Challenge with Ethanol, Dexamethasone and Corticotropin-Releasing Hormone

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          Abstract

          Neuroendocrine and behavioral profiles of group-housed rodents differ from those of singly-housed ones. Subordinate rats have elevated plasma corticosterone (CORT) concentration and impaired activity of the hypothalamic-pituitary-adrenal (HPA) axis compared to dominant cagemates. However, little is known about the effects of social hierarchy on other stress-related hormones. We examined plasma prolactin (PRL) and CORT responses to saline and ethanol (EtOH) injections, and 1 month later to dexamethasone (DEX) and corticotropin-releasing hormone (CRH) challenges of group- (triad) and single-housed male rats over a period of 225 days. Social status was determined from behaviors displayed upon initial triad housing. Subordinate rats had lower basal PRL and higher CORT compared to dominant rats. The injection of EtOH (1.25 g/kg) depressed PRL and elevated CORT levels significantly more than the saline injection only in dominant and singly-housed rats. DEX increased PRL levels, most strikingly in dominant rats, and suppressed CORT only in dominant rats. After CRH challenge, plasma CORT increased in all groups, subdominant and subordinate rats displaying blunted responses. Our data demonstrate that social rank and housing conditions affect plasma PRL and CORT concentrations, and modify responses to EtOH, possibly reflecting impairments of HPA axis regulation in socially-housed rats.

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          Most cited references46

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          Plasticity of the hippocampus: adaptation to chronic stress and allostatic load.

          The hippocampus is an important structure for declarative, spatial, and contextual memory and is implicated in the perception of chronic pain. The hippocampal formation is vulnerable to damage from seizures, ischemia, and head trauma and is particularly sensitive to the effects of adrenal glucocorticoids secreted during the diurnal rhythm and chronic stress. Adrenal steroids typically have adaptive effects in the short run, but promote pathophysiology when there is either repeated stress or dysregulation of the HPA axis. The damaging actions of glucocorticoids under such conditions have been termed "allostatic load", referring to the cost to the body of adaptation to adverse conditions. Adrenal steroids display both protective and damaging effects in the hippocampus. They biphasically modulate excitability of hippocampal neurons, and high glucocorticoid levels and severe acute stress impair declarative memory in a reversible manner. The hippocampus also displays structural plasticity, involving ongoing neurogenesis of the dentate gyrus, synaptogenesis under control of estrogens in the CA1 region, and dendritic remodeling caused by repeated stress or elevated levels of exogenous glucocorticoids in the CA3 region. In all three forms of structural plasticity, excitatory amino acids participate along with circulating steroid hormones. Glucocorticoids and stressors suppress neurogenesis in the dentate gyrus. They also potentiate the damage produced by ischemia and seizures. Moreover, the aging rat hippocampus displays elevated and prolonged levels of excitatory amino acids released during acute stress. Our working hypothesis is that structural plasticity in response to repeated stress starts out as an adaptive and protective response, but ends up as damage if the imbalance in the regulation of the key mediators is not resolved. It is likely that morphological rearrangements in the hippocampus brought on by various types of allostatic load alter the manner in which the hippocampus participates in memory functions and it is conceivable that these may also have a role in chronic pain perception.
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            Subordination stress: behavioral, brain, and neuroendocrine correlates.

            In mixed-sex rat groups consistent asymmetries in offensive and defensive behaviors of male dyads are associated with the development of dominance hierarchies. Subordinate males can be differentiated from dominants on the basis of both agonistic and non-agonistic behaviors, wound patterns, weight changes. Their behavior changes suggest chronic defensiveness and are also broadly isomorphic to many of the symptoms of depression; their voluntary alcohol consumption increases, and their life-spans are shortened. Both subordinate and dominant males tend to show organ change compared to non-grouped controls, with adrenal and spleen enlargement and thymus reduction. However, these changes appear to be more marked in subordinates, and only subordinates show reduced testes weights. Basal corticosterone (CORT) levels were sharply higher, and plasma testosterone (T) sharply lower, in subordinates compared to both dominants and controls, and reduced corticosterone binding globulin further enhanced free CORT for subordinates particularly. Many subordinates failed to show a normal CORT response to restraint stress. Subordinates also appear to show widespread changes in serotonin systems, with increased 5-HIAA/5-HT ratios in a number of brain areas, and alterations of 5-HT1A receptor binding at some sites. These changes suggest that subordination, a common and consistent feature of life for many animals living in social groups, may be a particularly relevant model for investigating the behavioral, neural and endocrine correlates of chronic stress.
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              Behavior and physiology of social stress and depression in female cynomolgus monkeys.

              The hypothesis that social subordination is stressful, and results in a depressive response in some individuals, was examined in socially housed female cynomolgus monkeys. Social status was manipulated such that half of the previously subordinate females became dominant and half of the previously dominant females became subordinate. Current subordinates hypersecreted cortisol, were insensitive to negative feedback, and had suppressed reproductive function. Current subordinates received more aggression, engaged in less affiliation, and spent more time alone than dominants. Furthermore, they spent more time fearfully scanning the social environment and displayed more behavioral depression than dominants. Current subordinates with a history of social subordination were preferentially susceptible to a behavioral depression response. The results of this experiment suggest that the stress of social subordination causes hypothalamic-pituitary-adrenal and ovarian dysfunction, and support the hypothesis that chronic, low-intensity social stress may result in depression in susceptible individuals.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2004
                February 2005
                25 February 2005
                : 80
                : 5
                : 332-342
                Affiliations
                aCenter of Alcohol Studies, Rutgers University, Piscataway, N.J. and bIRP, NIDA, NIH, Baltimore, Md., USA
                Article
                83682 Neuroendocrinology 2004;80:332–342
                10.1159/000083682
                15692218
                5136d05c-b4ce-4f3c-be63-0bda93803c81
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 2, Tables: 3, References: 65, Pages: 11
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Prolactin,Psychosocial stress,Ethanol,Behavior,Aggression,Adrenal steroids,Corticotropin-releasing hormone

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