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Unformatted text preview: Effects of Interleukin-1 and Lipopolysaccharide on Behavior of Mice in the Elevated Plus-Maze and Open Field Tests Artur H. Swiergiel and Adrian J. Dunn Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA. Abstract It has been postulated that infections, inflammatory processes and resulting cytokines may be causative factors in emotional disorders, including depression and anxiety. Support for this possibility has been sought in studies of animal behavior following administration of interleukin-1 (IL-1) and lipopolysaccharide (LPS). However, such treatments induce a variety of behavioral responses, collectively known as sickness behavior, some of which could affect the performance in tests used to assess anxiety and depression. Thus the effects of peripheral administration of IL-1 and LPS on the behavior of mice were studied in the elevated plus-maze (EPM) and the open field (OF). Mouse IL-1 (30, 100, 300, and 1000 ng) was injected intraperitoneally 30 or 60 min, and LPS (0.5, 1 and 5 g) 120 minutes before the tests. IL-1 and LPS induced dose-dependent decreases in open arm entries and the time spent on the open arms in the EPM, effects considered to reflect anxiety-like behavior. However, entries to all arms were also reduced in a dose-dependent manner, indicating a decrease in general activity. In the OF, IL-1 and LPS decreased the number of line-crossings in the center of the field, that can also be considered to reflect anxiety-like behavior. However, this effect was accompanied by a similar decrease in line-crossings in the periphery, as well as in rears and climbs. Thus the doses of IL-1 and LPS necessary to induce these effects also decreased locomotor activity in the EPM and OF. Therefore, the behavioral responses induced by IL-1 and LPS in the EPM and the OF considered to reflect anxiety must be interpreted in the light of this reduction in overall activity. Thus the results do not provide unequivocal support for the suggestion that LPS or IL-1 mediate anxiety. Nevertheless, because infections, endotoxins, and the ensuing cytokines cause alterations in CNS norepinephrine and serotonin, they may contribute to emotionality, and perhaps to anxiety. Introduction Administration of interleukin-1 (IL-1) and lipopolysaccharide (LPS) induces physiological changes like those associated with physical or psychogenic stressors in rats and mice (Connor et al., 1998;Dunn et al., 1999;Anisman et al., 2002). Both IL-1 and LPS activate brain norepinephrine and serotonin metabolism (Dunn, 1988;Kabiersch et al., 1988;Dunn, 2006), and activate the hypothalamic-pituitary-adrenal (HPA) axis so that plasma concentrations of ACTH and glucocorticoids are increased (Besedovsky et al., 1986;Dunn, 1988,2000)....
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- Spring '08