The role of midbrain 3α,5α-THP in mediating exploration, anxiety, social, and reproductive behavior

Abstract

Ovarian steroids, including 17β-estradiol (E2) and progesterone (P4) influence the onset and duration of reproductive behavior of female rodents. Separate lines of investigation also suggest that E2 and P4 influence exploratory, anxiety, and social behaviors. In addition to ovarian secretion, E2 and P4 are also neurosteroids produced de novo in brain. The midbrain ventral tegmental area (VTA), which is involved in motivation and reward, is an important brain area for mediating steroids' effects on reproductive behavior. As such, this chapter discusses research from our laboratory on the role, sources, and substrates of steroid hormones' modulation of exploratory, anxiety, social, and reproductive behaviors. The approach that we have used is manipulating, in the VTA, E2 and P4 and its metabolites, dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (3α,5α-THP), their de novo production, and subsequent effects on behavior via traditional actions at intracellular progestin receptors (PRs) and non-traditional substrates, such as GABAA, NMDA, and dopamine receptors. Endpoints examined include behavior in the open field, elevated plus maze, social choice, social interaction, and paced mating tasks and levels of E2 and progestins in serum, midbrain, hippocampus, striatum, and cortex. Manipulating 3α,5α-THP in the VTA influences exploration, anxiety, social and reproductive behavior, as well as neurosteroidogenesis in the VTA, hippocampus, and cortex. © 2008 Springer Netherlands.