Progestins can have a membrane-mediated action in rat midbrain for facilitation of sexual receptivity

In rats, progesterone (P) facilitates sexual receptivity by interacting with intracellular progestin receptors in the ventromedial hypothalamus (VMH). This experiment concerns whether P can also facilitate receptivity in rats by acting extragenomically within the ventral tegmental area (VTA). Ovariectomized rats (n = 10) with bilateral guide cannulas over the VMH and VTA were primed with 2 microg subcutaneous estradiol benzoate 44 hr prior to testing. After a pretest for sexual receptivity, animals received implants to the VMH of P, P conjugated to bovine serum albumin (P:BSA), or cholesterol control (CHOL), and were retested. Two hours later, animals were again tested for receptivity, and P, P:BSA, the P metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), or CHOL implants were applied to the VTA. Subjects were retested immediately, 30, 90, and 150 min later. Animals that received P in the VMH and had P, P:BSA, or 3alpha,5alpha-THP applied to the VTA exhibited facilitated receptivity at all time points compared with all other combination implants. That P:BSA and P were equally effective when applied to the VTA, but not the VMH, suggests that in the VTA P's membrane-mediated actions are sufficient to facilitate receptivity, whereas in the VMH they are not. Since the steroid (P) and its metabolite (3alpha,5alpha-THP) are similarly effective when applied to the VTA, given P application to the VMH earlier, P's effects in the VTA may be subsequent to metabolism and/or actions at GABA receptors. Overall, these data suggest that in rats P can act at the membrane of neurons within the VTA to modulate lordosis and that these effects may be subsequent to P's metabolism and/or actions at GABA receptors.