Inhibition of LiCl-induced conditioning of anticipatory nausea in rats following immune system stimulation: Comparing the immunogens lipopolysaccharide, muramyl dipeptide, and polyinosinic: polycytidylic acid

Abstract

The effects of the bacterial endotoxins, lipopolysaccharide (LPS) and muramyl dipeptide (MDP; Experiment 1), and the viral mimetic, polyinosinic: polycytidylic acid (poly I:C; Experiment 2), on the acquisition of “conditioned gaping” behavior in the rodent model of LiCl-induced anticipatory nausea were examined. Experimentally naïve adult male Long–Evans rats were injected (intraperitoneal, ip) with either 200μg/kg LPS, 1.6mg/kg MDP, or 0.9% saline (Experiment 1), or 4.0mg/kg poly I:C or 0.9% saline (Experiment 2), 90min prior to treatment with 127mg/kg LiCl or saline control and immediately placed into a distinctive context for 30min (repeated over 4 conditioning days, spaced 72h apart). On a drug-free test day (72h following conditioning day 4), each animal was re-exposed to the context for 10min, and orofacial and aversive behavioral responses were video recorded and analyzed. The results showed that pre-treatment with LPS, MDP (Experiment 1), or poly I:C (Experiment 2) prior to LiCl+context conditioning significantly impaired the establishment of conditioned gaping behavior, thus blocking the acquisition of anticipatory nausea. Results varied in regards to peripheral acute-phase response sickness behaviors, with significantly reduced weight loss in LPS-treated animals, less robust weight loss in poly I:C-treated animals, and no significant reductions in body weight in MDP-treated animals. The learning impairments observed in the current study suggest that endotoxin treatment with bacterial and viral endotoxin may have stronger central effects on learning and memory behavior, relative to peripheral effects on body weight and other sickness-related responses.