Lipopolysaccharide affects exploratory behaviors toward novel objects by impairing cognition and/or motivation in mice: Possible role of activation of the central amygdala

Lipopolysaccharide (LPS) produces a series of systemic and psychiatric changes called sickness behavior. In the present study, we characterized the LPS-induced decrease in novel object exploratory behaviors in BALB/c mice. As already reported, LPS (0.3–5 μg/mouse) induced dose- and time-dependent decreases in locomotor activity, food intake, social interaction, and exploration for novel objects, and an increase in immobility in the forced-swim test. Although the decrease in locomotor activity was ameliorated by 10 h postinjection, novel object exploratory behaviors remained decreased at 24 h and were observed even with the lowest dose of LPS. In an object exploration test, LPS shortened object exploration time but did not affect moving time or the frequency of object exploration. Although pre-exposure to the same object markedly decreased the duration of exploration and LPS did not change this reduction, LPS significantly impaired the exploration of a novel object that replaced the familiar one. LPS did not affect anxiety-like behaviors in open-field and elevated plus-maze tests. An LPS-induced increase in the number of c-Fos–immunoreactive cells was observed in several brain regions within 6 h of LPS administration, but the number of cells quickly returned to control levels, except in the central amygdala where the increase continued for 24 h. These results suggest that LPS most prominently affects object exploratory behaviors by impairing cognition and/or motivation including continuous attention and curiosity toward objects, and that this may be associated with activation of brain nuclei such as the central amygdala.

► LPS markedly decreases novel object exploratory behavior (NOEB) in BALB/c mice.
► The sustained decrease in NOEB is dissociated from an acute decrease in locomotion.
► A dose–response study shows that the decrease in NOEB is a primary response to LPS.
► LPS decreases NOEB by impairing continuous attention and/or curiosity toward an object.
► Sustained activation of the central amygdala may underlie the depressed exploration.