Exploratory, anti-anxiety, social, and sexual behaviors of rats in behavioral estrus is attenuated with inhibition of 3α,5α-THP formation in the midbrain ventral tegmental area

The progesterone (P4) metabolite and neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP) acts in the midbrain ventral tegmental area (VTA) to modulate lordosis of female rats. 3α,5α-THP also mediates exploratory, affective, and social behaviors; whether actions of 3α,5α-THP in the VTA mediate these behaviors is of interest. To elucidate the role of the VTA in mediating exploratory, affective, and social behaviors, the present study examined effects of inhibiting 3α,5α-THP formation in the VTA. Rats received intra-VTA infusions of either PK11195 (400 ng/μl, which inhibits de novo 3α,5α-THP production), indomethacin (10 μg/μl, which blocks metabolism of P4 to 3α,5α-THP), PK11195 and indomethacin together, or β-cyclodextrin vehicle and tested on a battery of anxiety (open field and elevated plus maze), social (partner preference and social interaction), and sexual (paced mating) tasks. Compared to rats infused with vehicle to the VTA, rats infused with inhibitor(s) demonstrated significant reductions in central entries in the open field, time on open arms of an elevated plus maze, time spent interacting with a conspecific, initiation and intensity of lordosis, sexual solicitations, and midbrain 3α,5α-THP levels. These findings suggest that actions of 3α,5α-THP in the VTA are important for mediating aspects of exploration, anxiety, and social behavior related to mating.