Allopregnanolone's attenuation of the lordosis-inhibiting effects of restraint is blocked by the antiprogestin, CDB-4124

• Published in: Pharmacology, biochemistry and behavior Vol. 122; pp. 16 - 19
• Main Authors: Uphouse, Lynda, Hiegel, Cindy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2014
• Subjects: Animals; Antiprogestin; Estradiol - analogs & derivatives; Estradiol - pharmacology; Female; Female rats; Male; Norpregnadienes - pharmacology; Ovariectomized; Posture - physiology; Pregnanolone - pharmacology; Progesterone receptor; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Restraint, Physical; Sexual behavior; Sexual Behavior, Animal - drug effects; Sexual Behavior, Animal - physiology; Stress; Female rats; Antiprogestin; Ovariectomized; Progesterone receptor; Stress; Sexual behavior
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2014.03.012

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 10μg estradiol benzoate. Two days later, rats received either 60mg/kg CDB-4124 or 20% DMSO/propylene glycol vehicle 1h before injection with 4mg/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. •Restraint reduced lordosis behavior of ovariectomized rats given estradiol benzoate.•Prior treatment with allopregnanolone protected against effects of restraint.•The antiprogestin, CDB-4124, attenuated the effect of allopregnanolone.