The neurosteroids, progesterone and 3α,5α-THP, enhance sexual motivation, receptivity, and proceptivity in female rats

The effects of progesterone (P) and the neurosteroid and P metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-onc (3 alpha,5 alpha-THP) on ovariectomized (ovx), estradiol-3-benzoate (EB)-primed rats on sexual motivation, receptivity, and proceptivity were examined. Changes in central P and 3 alpha,5 alpha-THP were measured following administration of EB, EB + P, EB + 3 alpha,5 alpha-TNP, or EB + inhibitor of 5 alpha-reductase or P metabolism (epostane and finasteride) + P (Expt. 1). Partner preference was measured as the duration of time females in these different hormonal treatments spent in proximity to a male vs, female conspecific (Expt. 2). Receptivity (lordosis quotients and ratings) and proceptivity (darting, hopping, ear wiggling, and pacing), for different hormone treatments were assessed (Expt. 3 and Expt. 3, respectively). Conditioned place preference following hormone treatments and paced mating enabled assessment of sexual motivation (Expt. 5). Central P and 3 alpha,5 alpha-THP were measured in various combinations of hormone/mating conditions (Expt. 6). Studies revealed that 3 alpha,5 alpha-THP has a significant role in these reproductive measures. Brain concentrations of 3 alpha,5 alpha-THP were significantly higher in animals receiving EB + P or EB + 3 alpha,5 alpha-THP compared to animals receiving EB alone, or EB + P in conjunction with an inhibitor of P metabolism. EB + P and EB + 3 alpha,5 alpha-THP significantly increased time spent in proximity to the male, receptivity and proceptivity. When administered to ovx, EB-primed rats, the progestin metabolite, 3 alpha,5 alpha-THP, had effects on these behaviors similar to P. Epostane, an inhibitor of P and 3 alpha,5 alpha-THP biosynthesis, and finasteride, an inhibitor of P metabolism to 3 alpha,5 alpha-TNP, administered to EB + P animals reduced male partner preference, preceptive, and receptive behaviors to levels seen in EB + vehicle animals. Notably, whole brain 3 alpha,5 alpha-THP levels were significantly increased and whole brain P levels were significantly reduced in paced mated rats compared to standard mated, and receptive non-mated animals. These studies suggest that P and 3 alpha,5 alpha-THP may have some common effects on reproductive behavior, e.g., sexual motivation, receptivity, and proceptivity. (C) 1998 Published by Elsevier Science B.V. All rights reserved.