Dose-related sex differences in the establishment of conditioned disgust (anticipatory nausea), and the effect of peripubertal and adult immune system stimulation with the endotoxin lipopolysaccharide (LPS) on learning and memory in the rat
Doctor of Philosophy
This thesis examined sex differences in the establishment of lithium chloride (LiCl) – induced conditioned disgust behavior (anticipatory nausea) to a distinct context, as well as, the establishment of conditioned place avoidance (CPA) using rodent models. Also examined were potential sex differences in response to treatment with the bacterial endotoxin, lipopolysaccharide (LPS), and its effect on learning and memory. In Chapter 2, male and female naïve Long-Evans rats were injected (intraperitoneally; i.p.) with either 200 µg/kg LPS or 0.9% (NaCl), 90 minutes prior to i.p. injections of either 128 mg/kg LiCl or 0.9% NaCl, and immediately placed into a distinctive context for 30 minutes (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 and forelimb flailing 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. In Chapter 3, the sex difference in conditioned gaping behavior found in Chapter 2 was explored further by examining potential dose-related effects. Once again, females displayed significantly higher frequencies of conditioned “gaping” behavior relative to males, in a dose-dependent manner. The results from Chapters 2 and 3 provide strong support for a sex difference in the onset and severity of nausea-related symptoms which is also observed among the human population. This provides a preclinical tool for testing the efficacy of anti-nausea treatments and noxious drug side-effects.
In Chapter 4, the effects of LPS pretreatment on the establishment of conditioned place avoidance (CPA) were examined. Female rats were also injected with LPS or saline during the peripubertal phase of development (6 weeks of age) and later pretreated with LPS again or saline in the classic two-chamber CPA paradigm. Results showed that while peripubertal LPS had no long-term effect on establishing CPA, it did interfere with the ability of a second LPS challenge in adulthood to block CPA, as was shown in subjects pretreated with LPS in adulthood only. The results of this study provide support for previous findings that suggest that stressors and/or immune challenges during this sensitive period of development can lead to long-lasting alterations in behavior.
Cloutier, Caylen J., "Dose-related sex differences in the establishment of conditioned disgust (anticipatory nausea), and the effect of peripubertal and adult immune system stimulation with the endotoxin lipopolysaccharide (LPS) on learning and memory in the rat" (2016). Electronic Thesis and Dissertation Repository. 4353.