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      Diurnal Variations in Lipopolysaccharide-Induced Sleep, Sickness Behavior and Changes in Corticosterone Levels in the Rat

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          Abstract

          Inoculation of rats with microorganisms or microbial constituents that activate host defense promotes non-rapid eye movement sleep (non-REMS) and suppresses REMS. In this study, we evaluated circadian influences on the effects of lipopolysaccharide (LPS) on sleep, sickness behavior and plasma corticosterone levels in the rat. Three sets of experiments were performed. In each, the animals were intraperitoneally injected with vehicle for LPS (30 µg/kg) during 2 consecutive days, at the beginning of either the circadian rest or the activity phase. In experiment 1, sleep-wake behavior and brain temperature were recorded, and in experiment 2, core body temperature, locomotor activity as well as food and water intake. In experiment 3, corticosterone blood levels were measured. The results show that LPS-evoked changes in temperature, sleep and other behavioral parameters depend markedly on the time of day LPS is administered. However, a direct comparison of the LPS data demonstrates that, except for sleep parameters, the absolute time course of the assessed parameters was rather similar between the rest and activity phases. These findings suggest that LPS evokes a state characterized by high temperature and low vigilance, which is reached independently of the circadian phase.

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          Behavioural effects of peripherally injected interleukin-1: role of prostaglandins.

          To investigate the possible mediation by prostaglandins of changes in behaviour induced by peripheral injection of interleukin-1 (IL-1), two types of behavioural tests were chosen, social exploration in mice and schedule-controlled behaviour in rats. Mice treated with 1 and 2.5 micrograms recombinant human IL-1 beta showed a time- and dose-dependent decrease in exploration of a juvenile conspecific. This effect was completely blocked by pretreatment with 10 mg/kg indomethacin or 10 mg/kg piroxicam, but not with 50 mg/kg aspirin. The disruption of operant responding induced by 5 micrograms IL-1 in rats was also suppressed by pretreatment with 5 mg/kg indomethacin or 10 mg/kg piroxicam. These results indicate that prostaglandins mediate the behavioural effects of peripherally injected IL-1.
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            Neuroendocrine rhythms

            Hormones are secreted with circhoral, circadian and seasonal periodicities. Circhoral pulsatility is a temporal code, many chronic and acute changes in neuroendocrine status being mediated by changes in the frequency of circhoral release. The identity of the neuronal circuits controlling circhoral release is not known. Circadian release of hormones occurs with a precise temporal order entrained to the light-dark cycle, synchronized to the activity/rest rhythm and generated by circadian oscillators, of which the suprachiasmatic nuclei are the most important. Seasonal rhythms are driven either by an endogenous circannual clock mechanism or by a process of photoperiodic time measurement which is dependent upon the duration of the nocturnal peak of the pineal hormone melatonin.
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              Effects of chronic infusion of lipopolysaccharide on food intake and body temperature of the rat.

              Unrestrained male Sprague-Dawley rats were infused for seven days with a low (2.45 micrograms/hr) or high (9.81 micrograms/hr) concentration of E. coli lipopolysaccharide (LPS). Compared to control (saline-infused) rats, food intake in the LPS-infused rats remained depressed for the entire infusion period. Despite this long-term suppression of food intake, fever was observed only during the daytime hours for the first two days of infusion. No significant increase in nighttime body temperature was observed. These data indicate that although tolerance to LPS occurred in rats with regard to its fever-inducing effect, tolerance with respect to its anorexigenic action did not occur.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2000
                June 2000
                23 June 2000
                : 71
                : 6
                : 375-385
                Affiliations
                Max Planck Institute of Psychiatry, Munich, Germany
                Article
                54558 Neuroendocrinology 2000;71:375–385
                10.1159/000054558
                10878499
                6b405a67-9dc6-4879-9ea5-93076c058746
                © 2000 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: 6, References: 34, Pages: 11
                Categories
                Stress, Corticotropin and Central Effects ofAdrenal Steroids

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Sleep,Neuroimmune interactions,Circadian Rhythms,Lipopolysaccharide,Sickness behavior,Stress

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