Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Abstract

Abstract17β-Estradiol (E 2 ) and progesterone (P 4 ) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P 4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), modulates lordosis of E 2 -primed rodents; 3α,5α-THP can also influence anxiety and social behaviors. To examine if 3α,5α-THP in the VTA mediates socio-sexual behaviors, we infused 3α,5α-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E 2 , P 4 , dihydroprogesterone (DHP), and 3α,5α-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3α,5α-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3α,5α-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3α,5α-THP, but neither E 2 nor P 4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3α,5α-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

Nigella sativa as an anti-inflammatory and promising remyelinating agent in the cortex and hippocampus of experimental autoimmune encephalomyelitis-induced rats

“…Behavior in the open field is used as a measure of exploration, anxiety, and locomotor behavior (Frye and Rhodes, 2008). The number of central square entries and the duration of time spent in the central square are measures of exploratory behavior and anxiety.…”

Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways

“…Mating induces 3α5α-THP biosynthesis [63][64][65][66] and, of ~50 genes that were upregulated in the midbrain VTA of mated vs. non-mated rats, many were those involved in steroid metabolism. Of the upregulated genes in the midbrain VTA of mated vs. non-mated rats, many were related to GABA, dopamine, and glutamate function and signal transduction.…”

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

“…Notably, infusions of 3α,5α-THP to the VTA of E 2 -primed, ovariectomized (OVX) rats results in facilitation of these appetitive and consummatory behaviors to levels which are akin to that of naturally-receptive rats (Frye and Rhodes, 2006b). We have recently demonstrated that 3α,5α-THP infusions to the VTA of diestrous rats facilitate appetitive and consummatory behavior to levels that are commensurate with naturally-receptive or OVX, E 2 -primed rats with 3α,5α-THP infusions to the VTA (Frye and Rhodes, 2008). Steroids' effects can be mediated via peripheral- and/or centrally-derived hormone formation (Melcangi and Panzica, 2006).…”