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Increasing 3,5-THP following inhibition of neurosteroid biosynthesis in the ventral tegmental area reinstates anti-anxiety, social and sexual behavior of naturally-receptive rats

C Frye, Psychology, The University at Albany - SUNY, Albany, United States
J Paris, Psychology, The University at Albany - SUNY, Albany, United States
M Rhodes, Psychology, The University at Albany - SUNY, Albany, United States

Correspondence: Cheryl Frye, Email: cafrye{at}albany.edu

Abstract

The progesterone metabolite and neurosteroid, 5-pregnan-3-ol-20-one (3,5-THP) has actions in the midbrain ventral tegmental area (VTA) to modulate lordosis, but its effects on other reproductively-relevant behaviors are not well understood. Effects on exploration, anxiety, and social behavior resulting from inhibition of 3,5-THP formation, as well as 3,5-THP enhancement, were investigated in the midbrain VTA. Naturally sexually-receptive, female rats (n=8-10/group) received infusions aimed at the midbrain VTA of vehicle, PK11195 (an inhibitor of neurosteroidogenesis) and/or indomethacin (an inhibitor of 3,5-THP formation from prohormones) and were subsequently infused with vehicle or FGIN 1-27 (a neurosteroidogenesis enhancer). Rats were then assessed in a behavioral battery that examined exploration (open field), anxiety (elevated plus maze), social (social interaction) and sexual (paced mating) behavior. Inhibition of 3,5-THP formation decreased exploratory, anti-anxiety, social and sexual behavior, as well as midbrain 3,5-THP levels. Infusions of FGIN 1-27 following 3,5-THP inhibition restored these behaviors and midbrain 3,5-THP levels to those commensurate of control rats that had not been administered inhibitors. These findings suggest that 3,5-THP formation in the midbrain VTA is may influence appetitive, as well as consummatory, aspects of mating behavior.