Repeated lipopolysaccharide exposure modifies immune and sickness behaviour response in an animal model of chronic inflammation

Abstract

Repeated lipopolysaccharide exposure is often used in longitudinal preclinical models of depression. However, the potential phenotypic differences from acute depression-mimicking effects are rarely described. This study compared chronic lipopolysaccharide administration of doses previously used in depression research to a new mode of escalating dose injections. Adult male BALB/c mice (n=8/group) were injected intraperitoneally with either a single 0.83 mg/kg dose, a repeated 0.1 mg/kg lipopolysaccharide dose or a dose which escalated weekly from 0.33 to 0.83 mg/kg lipopolysaccharide for six weeks. The escalating lipopolysaccharide group demonstrated most features of sickness behaviour such as weight loss and reduction in food intake every week, whilst this effect was not sustained in other groups. Moreover, only in the escalating lipopolysaccharide group did most peripheral plasma cytokines levels, measured using Luminex multiplex technology, such as interleukin-6, tumour necrosis factor α and interleukin-2 remain over three-fold elevated on the sixth week. In addition, exposure to escalating doses led to a reduction of neuroblast maturation in the dentate gyrus relevant for depression neurobiology. Therefore, this mode of injections might be useful in the studies attempting to replicate neurobiological aspects of the chronic inflammatory state observed in mood disorders.