Locomotor activity changes following lipopolysaccharide treatment in mice: a multivariate assessment of behavioral tolerance.

To determine the effects of repeated, acute endotoxin exposure on locomotor behavior, male laboratory mice were injected intraperitoneally with lipopolysaccharide (LPS: 50, 100 or 200 microg/kg) or saline vehicle on experimental Days 1, 4 and 7. At 2 h after each treatment, locomotor activity was assessed in a nonnovel, automated open-field apparatus (Digiscan) for 30 min. On Day 1, all horizontal and vertical activity measures were significantly reduced to near zero values by each dose of LPS. Behavioral tolerance to LPS formed rapidly, as locomotor activity of the treated groups did not differ from the control group on Days 4 or 7. In a second study, mice were given LPS (50, 100 or 150 microg/kg ip) or saline vehicle on two test days, 28 days apart. Activity was assessed, 1 h after injection, in a novel open field on the first test day and in a nonnovel open field on the second test day. Significant locomotor activity decrements were readily apparent in LPS-treated mice only in the nonnovel open field. This latter finding indicates that environmental novelty mediates, at least partially, the locomotor-reducing effects of LPS in mice.