Effects of interleukin-1beta and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests.

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-1beta and LPS on the behavior of mice were studied in the elevated plus-maze (EPM) and the open field (OF). Mouse IL-1beta (30, 100, 300, and 1000 ng) was injected intraperitoneally 30 or 60 min, and LPS (0.5, 1 and 5 microg) 120 min before the tests. IL-1beta 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-1beta 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-1beta and LPS necessary to induce these effects also decreased locomotor activity in the EPM and OF. Therefore, the behavioral responses induced by IL-1beta 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.