Anxiolytic Activity of Progesterone in Progesterone Receptor Knockout Mice

The study investigated the role of progesterone receptors (PRs) in the anxiolytic effects of progesterone using progesterone receptor knockout (PRKO) mice. It was found that the anxiolytic activity of progesterone was not diminished in PRKO mice compared to wild-type (WT) mice, indicating that PRs were not necessary for this effect. Interestingly, the anxiolytic effect was even larger in PRKO mice than in WT controls, although this difference was significant only at certain levels. This suggested that the anxiolytic effects of progesterone might be mediated through mechanisms other than PRs, possibly involving its metabolite allopregnanolone, which modulates GABAA receptors.