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      Corticosterone Synthesis Inhibitor Metyrapone Preserves Changes in Maternal Behavior and Neuroendocrine Responses during Immunological Challenge in Lactating Rats

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          Abstract

          Lactation is associated with profound behavioral and physiological adaptations in the mother that support reproductive success. These include neuroendocrine adaptation to stress that reduces anxiety-related behavior and emotional responsiveness. However, the way in which endogenous glucocorticoids secreted during immunological challenge influence the neuroendocrine system and behavior of lactating rats is not well understood. To evaluate the effects of glucocorticoids on the neuroendocrine response to suckling, maternal behavior and maternal anxiolysis, lactating female rats were treated with vehicle or metyrapone prior to the administration of a saline solution or a lipopolysaccharide (LPS) solution. LPS treatment reduced oxytocin and prolactin secretion during suckling and affected a variety of maternal behaviors, such as increasing the latency of retrieval a new nest, decreasing the number of pups gathered to the nest, increasing the latency of retrieving the first pup and decreasing the percentage of time spent in the arched-nursing position. In addition, the LPS treatment increased the baseline and avoidance latencies in an elevated T-maze. Pretreatment with metyrapone counteracted effects produced by LPS, including hormonal and behavioral responses in lactating rats. Taken together, our results indicate that stress induced by LPS treatment attenuates the neuroendocrine response to suckling, followed by disruption of maternal behavior and maternal anxiolysis in lactating female rats. These changes may be due to corticosterone release, as evidenced by the reversal of behavioral and neuroendocrine responses after immunological challenge in lactating rats that had been pretreated with metyrapone.

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          Most cited references61

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          Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat.

          The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.
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            Immune-neuro-endocrine interactions: facts and hypotheses.

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              Allostatic load, social status and stress hormones: the costs of social status matter

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2013
                June 2013
                06 February 2013
                : 97
                : 4
                : 322-330
                Affiliations
                aDepartment of Physiological Science, Federal University of Alfenas (UNIFAL), Alfenas, and bDepartment of Physiology, São Paulo University (USP), Ribeirão Preto, Brazil
                Author notes
                *Fabiana Cardoso Vilela, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, Centro, Alfenas, MG 37130-000 (Brasil), E-Mail facvilela@gmail.com
                Article
                346354 Neuroendocrinology 2013;97:322-330
                10.1159/000346354
                23295343
                82fadb61-b2e4-4b14-9526-561a4640dd09
                © 2013 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
                : 27 June 2012
                : 07 December 2012
                Page count
                Figures: 4, Pages: 9
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Lactation,Oxytocin,Prolactinߛ,Maternal anxiolysis,Maternal behavior

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