RU486 blocks effects of allopregnanolone on the response to restraint stress.

These experiments were designed to provide information about the potential involvement of progesterone receptors in the ability of allopregnanolone (3α-hydroxy-5α-pregnan-20-one) to reduce the lordosis-inhibiting effects of restraint stress. Ovariectomized Fischer rats were hormonally primed with 10 μg estradiol benzoate and 4 mg/kg allopregnanolone or vehicle. One hour before allopregnanolone, rats were injected with the progesterone receptor antagonist, RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), or vehicle. Four hours after allopregnanolone or vehicle, sexual behavior was examined before and after a 5-min restraint stress. Lordosis behavior of rats primed only with estradiol benzoate declined after the 5 min of restraint while allopregnanolone prevented this decline. RU486 attenuated the ability of allopregnanolone to prevent the restraint-induced decline in lordosis behavior. These findings are consistent with earlier suggestions that progesterone receptors are involved in allopregnanolone's ability to reduce the effects of restraint stress.