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      Cytokines and cognitive behavior.

      Neuroimmunomodulation
      Animals, Behavior, Animal, drug effects, Cognition, physiology, Cognition Disorders, immunology, Female, Interleukin-1, pharmacology, Maze Learning, Mice, Mice, Inbred C57BL, Motivation, Neuroimmunomodulation

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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-1beta 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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          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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