Automated home-cage monitoring as a potential measure of sickness behaviors and pain-like behaviors in LPS-treated mice

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 problematic. Hence, we used automated home-cage monitoring LABORAS to evaluate spontaneous 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 pharmacological intervention improved sickness behaviors in the open-field test as well as automated home-cage monitoring, confirming that automated home-cage monitoring could be potentially useful in pharmacological screening. Together, our results demonstrate that automated 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.

Curcumin Diethyl γ-Aminobutyrate, a Prodrug of Curcumin, for Enhanced Treatment of Inflammatory Pain

“…Sickness behaviors are a host response to pathogenic insults and inflammation that physiologically occur to fight infection. The responses manifest in several symptoms, including reduced physical ability, fever, fatigue, anxiety, depression, weight loss, changes in food, water intake, and sleep pattern. − Locomotor activity driven by exploratory behaviors has been used to indicate sickness and pain-like behaviors in LPS-induced mice . Intraperitoneal LPS administration to the mice reduces spontaneous and general locomotive behaviors, representing physical disability in humans .…”

“…Therefore, long-term observation covering day and night is necessary to capture mouse behaviors comprehensively. The use of LABORAS automated home-cage behavioral analysis for assessing sickness behaviors for long-duration was previously reported . Here, the effect of CUR-2GE on long-term locomotor activity covering day and night phases was investigated.…”

“…27−30 Locomotor activity driven by exploratory behaviors has been used to indicate sickness and pain-like behaviors in LPSinduced mice. 31 Intraperitoneal LPS administration to the mice reduces spontaneous and general locomotive behaviors, representing physical disability in humans. 31 In the present study, the effects of CUR-2GE on locomotor activity driven by exploratory behaviors were assessed in LPS-induced mice after treatment with 100 mg/kg curcumin or its equimolar dose of CUR-2GE.…”

“…31 Intraperitoneal LPS administration to the mice reduces spontaneous and general locomotive behaviors, representing physical disability in humans. 31 In the present study, the effects of CUR-2GE on locomotor activity driven by exploratory behaviors were assessed in LPS-induced mice after treatment with 100 mg/kg curcumin or its equimolar dose of CUR-2GE. The effect of compounds on exploratory behavior is shown by ethogram visualization (Figure 6A) and the duration and frequency of each behavior (Figure 6B−F).…”

“…The use of LABORAS automated home-cage behavioral analysis for assessing sickness behaviors for long-duration was previously reported. 31 Here, the effect of CUR-2GE on long-term locomotor activity covering day and night phases was investigated. The behavioral analysis was divided into several time slots, which are 0−2, 2−7, 7−12, and 12−24 h postcompound administration.…”