Evaluating sickness-induced anxiety versus lethargy at the behavioral and neuronal activity level

Abstract

In mammals, inflammatory responses to infections trigger adaptive behavioral changes collectively known as sickness behavior. Among these, lethargy protects the sick individual by conserving energy, and increased anxiety is believed to prevent exposure to threats. However, the characterization of these conflicting behavioral states in sickness could be an artifact of behavioral assessment, particularly in rodents. We adjusted existing behavioral testing and designed a new paradigm to disambiguate between increased lethargy versus increased anxiety. Our data indicate that in mice sickness induces a significant increase in lethargy but not in anxiety. Further supporting our behavioral results, at the neuronal level we found evidence that sickness activates anxiolytic rather than anxiogenic regions of the amygdala, including oxytocin receptor expressing neurons. Putative mechanisms by which sickness could activate CeA-OTR+ neurons were investigated.