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

Abstract

The effects of progesterone (P) and the neurosteroid and P metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) on ovariectomized (ovx), estradiol-3-benzoate (EB)-primed rats on sexual motivation, receptivity, and proceptivity were examined. Changes in central P and 3alpha,5alpha-THP were measured following administration of EB, EB+P, EB+3alpha,5alpha-THP, or EB+inhibitor of 5alpha-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. 4, respectively). Conditioned place preference following hormone treatments and paced mating enabled assessment of sexual motivation (Expt. 5). Central P and 3alpha,5alpha-THP were measured in various combinations of hormone/mating conditions (Expt. 6). Studies revealed that 3alpha,5alpha-THP has a significant role in these reproductive measures. Brain concentrations of 3alpha, 5alpha-THP were significantly higher in animals receiving EB+P or EB+3alpha,5alpha-THP compared to animals receiving EB alone, or EB+P in conjunction with an inhibitor of P metabolism. EB+P and EB+3alpha, 5alpha-THP significantly increased time spent in proximity to the male, receptivity and proceptivity. When administered to ovx, EB-primed rats, the progestin metabolite, 3alpha,5alpha-THP, had effects on these behaviors similar to P. Epostane, an inhibitor of P and 3alpha,5alpha-THP biosynthesis, and finasteride, an inhibitor of P metabolism to 3alpha,5alpha-THP, administered to EB+P animals reduced male partner preference, proceptive, and receptive behaviors to levels seen in EB+vehicle animals. Notably, whole brain 3alpha, 5alpha-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 3alpha,5alpha-THP may have some common effects on reproductive behavior, e.g., sexual motivation, receptivity, and proceptivity.