Attractiveness of illness-associated odorant cues in female rats is modulated by ovarian hormones, but not associated with pro-inflammatory cytokine levels

Odorant cues released by rodents play a key role in mate preference/selection. The goal of the following series of studies was to determine the impact of acute illness, and the potential role of the inflammatory response, on the release of illness-associated odor cues from female rats. Adult female Sprague-Dawley rats were injected with lipopolysaccharide (LPS, 100 μg/kg) and their soiled bedding was used as a stimulus to naïve male odor recipients. While odored bedding from sick males elicited a robust avoidance response evidenced by decreased sniffing, avoidance and burying behavior, odored bedding from sick females elicited only a reduction in sniffing, indicating a reduction in odor attractiveness. Odor cues from ovariectomized, but not sham-operated females decreased sniffing behavior and increased avoidance in male odor recipients. Acute estradiol benzoate (EB, 20 μg/kg) replacement into ovariectomized females restored the investigatory response of male recipients toward odor cues, while LPS administration into ovariectomized oil or EB treated females had little impact on odor attractiveness. Measurement of cytokines in both brain (the paraventricular nucleus of the hypothalamus) and blood from female odor donors indicated increased expression of TNF-α, IL-1β, and IL-6 following LPS, which was not affected by EB treatment. These findings illustrate a critical sexual dimorphism by demonstrating that acute illness reduces the attractiveness of female odor, whereas odor cues from sick males are highly aversive. Moreover, the attractiveness of female odor appears to be associated with circulating ovarian hormone levels, but not central or peripheral inflammatory cytokines.