Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors.

Blocking progesterone's metabolism to 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) with finasteride, a 5 alpha-reductase inhibitor, and effects on anxiolytic, exploratory, and antinociceptive behaviors of rats in behavioral estrus were examined. Rats in behavioral estrus received finasteride systemically (SC), to the hippocampus, or to control implant sites, the nucleus accumbens (NA) or ventral tegmental area (VTA), and were tested in horizontal crossing, open-field, elevated plus-maze, emergence, holeboard, social interaction, tailflick, pawlick, and defensive freezing tasks. Finasteride, SC or intrahippocampally, reduced 3 alpha,5 alpha-THP in the hippocampus relative to vehicle implants or finasteride to the NA or VTA. Systemic or intrahippocampal finasteride decreased central entries in the open field and open-arm time on the elevated plus-maze and increased freezing in response to shock relative to vehicle. Finasteride to the hippocampus decreased emergence latencies and increased social interaction, pawlick, and tailflick latencies relative to all other groups. Finasteride to the hippocampus of rats in behavioral estrous decreased anxiolysis and enhanced exploration and analgesia. In summary, these data demonstrate that decreases in anxiolytic behavior of behavioral estrous rats can be produced by reductions in 3 alpha,5 alpha-THP in the hippocampus, which suggest that elevations in 3 alpha,5 alpha-THP in the hippocampus may give rise to anxiolysis seen during behavioral estrus.