A brief restraint experience reduces
lordosis behavior in ovariectomized females that have been hormonally primed with
estradiol benzoate. The addition of
progesterone to the priming prevents the
lordosis inhibition. Based on prior studies with an inhibitor of
progesterone metabolism, we have implicated the intracellular
progesterone receptor, rather than
progesterone metabolites, as responsible for this protection. However, the
progesterone metabolite,
allopregnanolone (3α-hydroxy-5α-pregnan-20-one), also prevents
lordosis inhibition after restraint. In a prior study, we reported that the
progestin receptor antagonist,
RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), attenuated the effect of
allopregnanolone. Because
RU486 can also block the
glucocorticoid receptor, in the current studies, we evaluated the effect of the
progestin receptor antagonist,
CDB-4124 (17α-acetoxy-21-methoxy-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione), which is relatively devoid of antiglucocorticoid activity. Ovariectomized, Fischer rats were injected with 10 μg
estradiol benzoate. Two days later, rats received either 60 mg/kg
CDB-4124 or 20%
DMSO/
propylene glycol vehicle 1 h before injection with 4 mg/kg
allopregnanolone. After a pretest to confirm sexual receptivity, rats were restrained for 5min and immediately tested for sexual behavior.
Lordosis behavior was reduced by the restraint and attenuated by
allopregnanolone. Pretreatment with
CDB-4124 reduced
allopregnanolone's effect. These findings support prior suggestions that allopreganolone reduces the response to restraint by mechanisms that require activation of the intracellular
progesterone receptor.