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      Cytokines and Cognitive Behavior

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          Abstract

          Proinflammatory cytokines help orchestrate host responses to infection and are a major communication link between peripheral immunity and the CNS. These cytokines initiate a number of CNS events that culminate in both physiological and behavioral changes. Peripheral IL-1β also affects information processing. A series of experiments examining the effect of learning intensity, motivation, and cytokine dose are reported. Using a well-established Morris water maze (MWM) system with female C57BL/6 mice, we report that (1) IL-1 (100 ng/mouse, i.p.) has no effect on MWM learning when mice are subjected to a spaced as opposed to a massed learning protocol; (2) water temperature is critical to the IL-1 effect on learning insofar as IL-1 interferes with learning in a warm-water but not a cold-water maze, and (3) higher doses (1,000 ng/mouse, i.p.) of IL-1 in experimental systems known to produce the IL-1-induced learning deficit with lower doses (100 ng/mouse, i.p.) show consistent facilitation, not impairment, of learning.

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          Most cited references 7

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          Spatial localization does not require the presence of local cues

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            Effects of interleukin-1 receptor antagonist on the behavioral effects of lipopolysaccharide in rat.

            To investigate the role of interleukin-1 (IL-1) in lipopolysaccharide (LPS)-induced sickness behavior, rats were injected with recombinant human interleukin-1 receptor antagonist (IL-1ra), an endogenous cytokine able to block most of the biological effects of IL-1 both in vivo and in vitro. Intraperitoneal injection of IL-1ra (3 mg/rat) attenuated the depressive effect of LPS (250 micrograms/kg) on social exploration and body weight when both treatments were injected peripherally. Intracerebroventricular injection of IL-1ra (60 micrograms/rat) did not block the effects of peripherally injected LPS. These data indicate that the peripherally mediated effects of IL-1 account for a significant part of LPS-induced sickness behavior.
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              Lipopolysaccharide and interleukin-1 depress food-motivated behavior in mice by a vagal-mediated mechanism.

              In order to assess the role of vagal nerve afferents in the decrease in food-motivated behavior induced by proinflammatory cytokines, the effects of lipopolysaccharide (LPS, 400 micrograms/kg ip) and recombinant human interleukin-1 beta (IL-1, 750-1500 ng/mouse ip) were tested on nose poke for food in vagotomized and sham-operated mice. Subdiaphragmatic vagotomy attenuated the decrease in response rate induced by IL-1 and LPS. These results suggest that the peripheral immune message is transmitted to the brain via a neural rather than a humoral pathway.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                978-3-8055-6766-4
                978-3-318-00353-6
                1021-7401
                1423-0216
                1998
                August 1998
                04 September 1998
                : 5
                : 3-4
                : 160-165
                Affiliations
                Midwest Research Institute, Kansas City, Mo., USA
                Article
                26332 Neuroimmunomodulation 1998;5:160–165
                10.1159/000026332
                9730681
                © 1998 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.

                Page count
                Figures: 4, References: 27, Pages: 6
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