Pregnane xenobiotic receptor knockout rats show decrements in exploratory, anti-anxiety, social, & sexual behaviors

Abstract
Progestogens are well known to mediate reproductive cycles. However, the effects and mechanisms by which these processes occur are not completely understood. There are variations in progestogens over the estrous cycle of rodents, such that increased levels of progesterone and metabolites coincide with periods of increased exploration, activity, social engagement, and a greater likelihood of mating. Progesterone is secreted by ovaries and in brain areas where the necessary enzymes are localized and where there is de novo production of progestogens. The midbrain ventral tegmental area is an important brain region for mediating sexual receptivity of female rodents. Progestogens have actions in this brain area, the enzymes necessary to metabolize progesterone are localized to this region, and de novo production occurs here. In a genebank analyses of tissue from midbrain, the prenane xenobiotic receptor (PXR) was identified. Here, we utilize PXR knock out rats (PXR KO) and Sprague Dawley wild type controls to test the hypothesis that PXR is involved in natural estrous cycle variations in anxiety behavior, exploration, social, and/or sexual behavior. These behaviors were compared between PXR KO rats and their wildtype counterparts in behavioral estrous. We hypothesized that if the natural rise in progestogen-sensitive anxiety, exploration, social, and sexual behavioral estrous requires action through PXR then there would be decrements in these behaviors among PXR KO compared, to wildtype, rats. Further, we expected that these behavioral decrements would be amplified when a primary source of progestogens, the ovaries, were removed. We predicted that decrements in cycling effects of progestogens would be even more salient in ovariectomized PXR KO and wild type rats that would be more reliant on central PXR for production of progestogens to mediate behavioral responses. A similar pattern of results was revealed among proestrous and ovariectomized PXR rats to have less exploration in the open field, make fewer entries to the open arms in the plus maze, and to have fewer social and sexual interaction compared to their wild type counterparts.