Abstract:
The use of endotoxin, such as lipopolysaccharide (LPS) as a model of sickness behavior,
has attracted recent attention. To objectively investigate sickness behavior along with its
pain-like behaviors in LPS-treated mice, the behavioral measurement requires accurate
methods, which reflects clinical relevance. While reflexive pain response tests have been
used for decades for pain assessment, its accuracy and clinical relevance remain problem atic. Hence, we used automated home-cage monitoring LABORAS to evaluate spontane ous locomotive behaviors in LPS-induced mice. LPS-treated mice displayed sickness
behaviors including pain-like behaviors in automated home-cage monitoring characterized
by decreased mobile behaviors (climbing, locomotion, rearing) and increased immobility
compared to that of the control group in both short- and long-term locomotive assessments.
Here, in short-term measurement, both in the open-field test and automated home-cage
monitoring, mice demonstrated impaired locomotive behaviors. We also assessed 24 h
long-term locomotor activity in the home-cage system, which profiled the diurnal behaviors
of LPS-stimulated mice. The results demonstrated significant behavioral impairment in
LPS-stimulated mice compared to the control mice in both light and dark phases. However,
the difference is more evident in the dark phase compared to the light phase owing to the
nocturnal activity of mice. In addition, the administration of indomethacin as a pharmacologi cal intervention improved sickness behaviors in the open-field test as well as automated
home-cage monitoring, confirming that automated home-cage monitoring could be poten tially useful in pharmacological screening. Together, our results demonstrate that auto mated home-cage monitoring could be a feasible alternative to conventional methods, such
as the open-field test and combining several behavioral assessments may provide a better
understanding of sickness behavior and pain-like behaviors in LPS-treated mice.
