Differences in fatigue-like behavior in the lipopolysaccharide and poly I:C inflammatory animal models, 2021, Foster et al

Highlights

• LPS and poly I:C administration induced systemic inflammation.
• LPS induced ‘sickness behaviors’, not observed poly I:C-treated animals.
• LPS produces ‘sickness behaviors’ similar to a human fatigue phenotype.

Abstract
Central fatigue is a condition associated with impairment of the central nervous system often leading to the manifestation of a range of debilitating symptoms. Fatigue can be a consequence of systemic inflammation following an infection. Administration of lipopolysaccharide (LPS) and polyriboinosinicolyribocytidlic (poly I:C) to animals can induce systemic inflammation by mimicking a bacterial or viral infection respectively and therefore have been used as models of fatigue.

We evaluated a range of phenotypic behaviors exhibited in the LPS and poly I:C animal models to assess whether they adequately replicate fatigue symptomology in humans. In addition to standard observation- and intervention-based behavioral assessments, we used powerful in-cage monitoring technology to quantify rodent behavior without external interference. LPS and poly I:C treated Sprague Dawley rats displayed ‘sickness behaviors’ of elevated temperature, weight loss and reduced activity in the open field test and with in-cage monitoring within 24 h post-treatment, but only LPS-treated rats displayed these behaviors beyond these acute timepoints. Once sickness behavior diminished, LPS-treated rats exhibited an increase in reward-seeking and motivation behaviors.

Overall, these results suggest that the LPS animal model produces an extensive and sustained fatigue-like phenotype, whereas the poly I:C model only produced acute effects. Our results suggest that the LPS animal model is a more suitable candidate for further studies on central fatigue-like behavior.

Open access, https://www.sciencedirect.com/science/article/pii/S0031938421000391