Inhibition of 5alpha-reductase enzyme or GABA(A) receptors in the VMH and the VTA attenuates progesterone-induced sexual behavior in rats and hamsters.

Progesterone (P) to the ventromedial hypothalamus (VMH) and the ventral tegmental area (VTA) of ovariectomized (OVX), estradiol benzoate (EB)-primed rats and hamsters produces female sexual behavior similar to that seen in proestrous, receptive rodents. Because P's 5alpha-reduced metabolites can have facilitative effects on female sexual receptivity through actions at GABA(A)/benzodiazepine receptor complexes (GBRs), the role of 5alpha-reductase and GBRs in the VMH and the VTA was investigated. In Experiment 1, 5alpha-reductase immunoreactivity (5alpha-red-IR) and GBR immunoreactivity (GBR-IR) in the VMH and the VTA of OVX, EB (10 microg) and P (500 microg)-primed rats and hamsters was examined. More 5alpha-red-IR and GBR-IR was seen in the VMH and the VTA of receptive (EB and P-primed) compared to non-receptive (sesame oil vehicle) rodents. In Experiment 2, OVX, EB and P-primed rats and hamsters received implants of finasteride, a 5alpha-reductase inhibitor, or no implants to the VMH and the VTA and were tested for sexual receptivity with a male. Ovariectomized EB and P-primed rats and hamsters receiving finasteride to the VMH and the VTA had decreased lordosis compared to rodents receiving control implants to the VMH and the VTA. In Experiment 3, OVX, EB and P-primed rats and hamsters received infusions of picrotoxin, a GBR antagonist, or vehicle infusion to the VMH and the VTA and were tested for sexual receptivity with a male. Ovariectomized EB and P-primed rats and hamsters receiving picrotoxin to the VMH and the VTA had decreased lordosis compared to rodents receiving vehicle infusions to the VMH and the VTA. These data suggest that 5alpha-reductase and GBRs are present in the VMH and VTA, and that inhibiting 5alpha-reductase activity or blocking GBRs in the VMH and the VTA attenuates EB+P-primed sexual receptivity of OVX rats and hamsters.