Rodent sex differences in disgust behaviors (anticipatory nausea) conditioned to a context associated with the effects of the toxin LiCl: Inhibition of conditioning following immune stimulation with lipopolysaccharide

•Male and female rats condition disgust behaviors to a distinct context•Adult female rats condition significantly stronger disgust behaviors, relative to male rats•Male rats showed significantly stronger acute-phase behavioral responses to lipopolysaccharide treatment, relative to females•Systemic lipopolysaccharide blocks conditioned disgust (i.e., anticipatory nausea) in male and female rodents

This study examined sex differences in the establishment of lithium chloride (LiCl)-induced conditioned disgust behavior (anticipatory nausea) to a distinct context in adult male and female rats. Also examined were potential sex differences in response to treatment with the bacterial endotoxin, lipopolysaccharide (LPS), and its effect on learning and memory. Twenty-nine male and 31 female naïve Long-Evans rats were injected (intraperitoneally; i.p.) with either 200 μg/kg LPS or 0.9% (NaCl), 90 min prior to i.p. injections of either 128 mg/kg LiCl or 0.9% NaCl, and immediately placed into a distinctive context for 30 min (repeated over 4 conditioning days, spaced 72 h apart). 72 h following the final conditioning day, each subject was re-exposed to the context on a drug-free test day where orofacial and somatic behaviors were recorded. Results showed that LiCl-treated females conditioned stronger disgust reactions, relative to LiCl-treated males, as evidenced by significantly higher frequencies of conditioned “gaping” behavior (p < 0.02) and forelimb flailing (p < 0.01) in females. Pre-treatment with LPS during conditioning led to strong inhibition of conditioned disgust behavior, to levels that did not significantly differ from controls. Although there was no apparent sex difference in the degree of inhibition produced by LPS in this context-based rodent disgust model, males did exhibit significantly greater 24 h body weight losses following LPS injections on the first two conditioning days, relative to females. The results of the current study provide strong evidence for a sex difference in the establishment of anticipatory nausea, as well as, evidence for a sex difference in the acute-phase response to endotoxin treatment.