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The role of sex and estrous phase in the conditioning of toxin-induced disgust reactions (anticipatory nausea) to a novel context were examined in adult rats. Conditioned oral gaping responses have been shown to be a reliable index of nausea in rats. In Experiment 1 male and female rats were injected with LiCl (0, 64, 96, or 128 mg/kg) on each of 4 conditioning trials (72 h apart) and then placed in a novel context for 30 min. 72 h following the last conditioning trial each animal was re-exposed to this context in a toxin-free state for 10 min and disgust responses (gapes, forelimb flails, chin rubs, and paw treads) were scored from video records. A significant toxin dose-related monotonic increase in conditioned gaping showed a significantly greater increase in females, relative to males. In Experiment 2 female rats were conditioned, using the same paradigm, on either diestrus or proestrus days (trials 96 h apart) with LiCl (96 mg/kg) or saline control injections. Disgust responses were recorded on each of the 4 conditioning trials and a toxin-free test trial. Significant increases in conditioned disgust were obtained on proestrus relative to diestrus days on the toxin-free test trial. However no significant estrous cycle differences in disgust responding were obtained on the acquisition trials. The sex difference in conditioned gaping and the increased conditioned disgust responses in proestrus suggest that increased levels of estradiol likely enhance the strength of the association of the toxin-induced nausea with the novel context in rats.Conditioned oral gaping responses are a reliable index of nausea in rats.Female rats acquire higher levels of toxin-induced conditioned gaping to a novel context than males.Female rats acquire higher levels of toxin-induced conditioned gaping to a novel context in proestrus relative to diestrus.Higher levels of endogenous estradiol likely enhance the context conditioning of disgust responses in female rats.