RU486 facilitates or disrupts the sensitization of sexual behaviors by estradiol in the ovariectomized Long-Evans rat: Effect of timecourse.

An acute injection of estradiol benzoate (EB) to the ovariectomized (OVX) rat activates low levels of lordosis, and subsequent progesterone (P) administration augments lordosis and recruits a complete pattern of sexual behavior including appetitive behaviors (e.g., hops/darts and solicitations). However, repeated injections of 5μg or 10μg EB (but not 2μg EB), administered every 4days to sexually-experienced OVX rats results in a behavioral sensitization, such that lordosis quotients (LQs) and appetitive behaviors progressively increase. We have shown that adrenal P does not play a critical role because behavioral sensitization to EB is not prevented by adrenalectomy. Here we tested whether P receptors play a role by examining the effect of chronic administration of the P receptor antagonist RU486 at a dose that reliably inhibits sexual behavior in fully primed OVX rats. Females were treated with EB (5 or 10μg), and 5mg RU486 dissolved in 0.4mL vehicle (VEH; 80% sesame oil, 15% benzyl benzoate, 5% benzyl alcohol) 48h and 5h prior to each of 7 tests, respectively, occurring at 4-day intervals in unilevel 4-hole pacing chambers. Control animals were treated with 2, 5, or 10μg EB+VEH. As expected, sensitization did not occur in females treated with 2μg EB+VEH, and those females received fewer intromissions and ejaculations than all other groups. RU486 did not prevent the sensitization of LQ, moderate and high lordosis magnitudes (LM2 and LM3) or appetitive sexual behaviors on early tests, and in fact potentiated appetitive behaviors, LQ, LM2 and LM3, consistent with its facilitative actions in females treated with EB-alone, as we and others have reported previously. However, despite the initial facilitation, blocking P receptors by chronic administration of RU486 inhibited the maintenance of behavioral sensitization to EB.