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In the VTA, the formation and actions of one progestogen, 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (3\u03b1,5\u03b1\u2010THP<\/jats:styled-content>), are necessary and sufficient to facilitate sexual responding (measured by lordosis) of female rodents. Although 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content> can be produced after metabolism of ovarian progesterone, 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content> is also a neurosteroid produced de novo<\/jats:italic> in brain regions, such as the VTA<\/jats:styled-content>. There can be dynamic changes in 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content> production associated with behavioural experience, such as mating. Questions of interest are the sources and targets of 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content>. Regarding sources, the pregnane xenobiotic receptor (PXR<\/jats:styled-content>) may be a novel factor involved in 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content> metabolism in the VTA<\/jats:styled-content> (as well as a direct target of 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content>). We have identified PXR<\/jats:styled-content> in the midbrain of female rats, and manipulating PXR<\/jats:styled-content> in this region reduces 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content> synthesis and alters lordosis, as well as affective and social behaviours. Regarding targets, recent studies have focused on the role of membrane progestin receptors (mPR<\/jats:styled-content>s). We have analysed the expression of two of the common forms of these receptors (mPR<\/jats:styled-content>\u03b1\/paqr7 and mPR<\/jats:styled-content>\u03b2\/paqr8) in female rats. The expression of mPR<\/jats:styled-content>\u03b1 was observed in peripheral tissues and brain areas, including the hypothalamus and midbrain. The expression of mPR<\/jats:styled-content>\u03b2 was only observed in brain tissues and was abundant in the midbrain and hypothalamus. To our knowledge, studies of these receptors in mammalian models have been limited to expression and regulation, instead of function. One question that was addressed was the functional effects of progestogens via mPR<\/jats:styled-content>\u03b1 and mPR<\/jats:styled-content>\u03b2 in the midbrain of hormone\u2010primed rats for lordosis. Studies to date suggest that mPR<\/jats:styled-content>\u03b2 may be an important target of progestogens in the VTA<\/jats:styled-content> for lordosis. Taken together, the result of these studies demonstrate that PXR<\/jats:styled-content> is involved in the production of 3\u03b1,5\u03b1\u2010THP<\/jats:styled-content> in the midbrain VTA<\/jats:styled-content>. Moreover, mPR<\/jats:styled-content>s may be a target for the actions of progestogens in the VTA<\/jats:styled-content> for lordosis.<\/jats:p>","DOI":"10.1111\/jne.12105","type":"journal-article","created":{"date-parts":[[2013,9,12]],"date-time":"2013-09-12T15:37:04Z","timestamp":1379000224000},"page":"1002-1011","source":"Crossref","is-referenced-by-count":18,"title":["Pregnane Xenobiotic Receptors and Membrane Progestin Receptors: Role in Neurosteroid\u2010Mediated Motivated Behaviours"],"prefix":"10.1111","volume":"25","author":[{"given":"C. A.","family":"Frye","sequence":"first","affiliation":[{"name":"Department of Chemistry The University of Alaska\u2013Fairbanks Fairbanks AK USA"},{"name":"Institute of Artic Biology The University of Alaska\u2013Fairbanks Fairbanks AK USA"},{"name":"IDeA Network of Biomedical Excellence (INBRE) The University of Alaska\u2013Fairbanks Fairbanks AK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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