Estrogen is necessary for 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) infusion to the ventral tegmental area to facilitate social and sexual, but neither exploratory nor affective behavior of ovariectomized rats.

The progesterone metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP, allopregnanolone), acts in the ventral tegmental area (VTA) to facilitate exploratory, anti-anxiety, and socio-sexual behavior among ovariectomized (OVX), estrogen (E(2))-primed rats and gonadally-intact rats with high (proestrus) or low (diestrus) endogenous E(2) levels. The extent to which E(2) is required for these effects of 3alpha,5alpha-THP is not known. OVX rats were primed with systemic 17beta-estradiol (10 microg) or oil vehicle and were infused 44 h later with 3alpha,5alpha-THP (100 ng) or beta-cyclodextrin vehicle to the VTA, substantia nigra (SN), or central grey (CG). Rats were assessed in a battery of exploratory (open field), anxiety (elevated plus maze), social (partner preference, social interaction), and sexual (paced mating) tasks. E(2)-priming was necessary for 3alpha,5alpha-THP infusions to facilitate social interaction and mating and midbrain 3alpha,5alpha-THP levels were higher among E(2)-compared to vehicle-primed rats. Irrespective of E(2)-priming, rats infused with 3alpha,5alpha-THP to the VTA, but not SN or CG, demonstrated increased exploration in an open field, anti-anxiety behavior on an elevated plus maze, and preference for a male. Thus, actions of 3alpha,5alpha-THP in the VTA to enhance social and sexual behaviors were reliant on E(2) but increases in exploratory and anti-anxiety behavior were not.