Differential behavioral, physiological, and hormonal sensitivity to LPS challenge in rats

Silvia Bison¹, Lucia Carboni¹, Roberto Arban¹, Simon Bate², Philip A Gerrard¹, Maria Razzoli¹

¹Department of Biology, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Verona, Italy; ²Statistical Sciences, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM195AW, UK

Abstract: In animals, systemic administration of lipopolysaccharide (LPS) induces a characteristic set of responses that has been termed sickness behavior. In the present study, the effects of a wide dose range of LPS injections on behavior and physiology were examined in rats. Male rats were injected IP with either saline or LPS (1, 5, 15, 50, 125, or 250 μg/kg). Body temperature, body weight, and home-cage activity were monitored over 24 h after injection. Behaviorally the social interaction and the saccharin preference tests were assessed at 2 and 24 h post-injection, respectively. Further animals were treated with LPS to assess hypothalamic–pituitary adrenal (HPA) axis and immune system responses 2 h post-injection. LPS significantly reduced body weight (1 μg/kg and above), increased ACTH (15 μg/kg and above) and serum corticosterone levels (5 μg/kg and above). In addition LPS raised serum interleukins (5 μg/kg and above) and tumor necrosis factor-alpha (1 μg/kg and above). Social behavior and preference for saccharin were significantly decreased at all doses of LPS tested (1–250 μg/kg) while a robust reduction in home-cage activity was observed starting at 15 μg/kg. The present finding suggests that LPS caused profound behavioral alterations and stimulation of the immune system even at very low doses.

Keywords: sickness behavior, lipopolysaccharide, cytokines, ACTH, corticosterone, social interaction