Anticonvulsant activity of progesterone and neurosteroids in progesterone receptor knockout mice

Many of the biological actions of progesterone are mediated through the progesterone receptor (PR), a nuclear transcription factor. Progesterone is well recognized to protect against sei-zures in animal models. Although this activity has been attrib-uted to the progesterone metabolite allopregnanolone, a GABAA receptor-modulating neurosteroid with anticonvulsant properties, PRs could also play a role. Here, we used PR knockout (PRKO/) mice bearing a targeted deletion of the PR gene that eliminates both isoforms of the PR to investi-gate the contribution of the PR to the anticonvulsant activity of progesterone. The protective activity of progesterone was examined in female and male homozygous PRKO mice and isogenic wild-type controls in the pentylenetetrazol (PTZ), maximal electroshock, and amygdala-kindling seizure mod