P-3-BSA, but not P-11-BSA, implants in the VTA rapidly facilitate receptivity in hamsters after progesterone priming to the VMH.

Recent evidence suggests that progesterone (P) may have behaviorally relevant actions on neuronal membranes in the ventral midbrain. In the present experiments, we exploited the rapid time course predicted for non-genomic actions of steroid hormones. Ovariectomized hamsters were implanted with chronic guide cannulae, one aimed above the ventromedial hypothalamus (VMH) and the other over the contralateral ventral tegmental area (VTA). The following week animals were estrogen-primed (10 micrograms estradiol benzoate) and pre-tested for sexual receptivity 2 h after a P or P conjugated to the macromolecule bovine serum albumin (P-3-BSA) containing tube was applied to the VMH. P-3-BSA binds well to neuronal membranes, but does not penetrate them because of the large size of the BSA molecule. After the pre-test, the opposite hormone-containing insert was applied to the VTA and hamsters were tested again for sexual receptivity 5 min after this implantation. The following week, the contents of the tubes were reversed. Receptivity only occurred when P was applied to the VMH and 2 h later P-3-BSA was applied to the VTA; the reverse treatment was ineffective. These data indicate that P is capable of rapidly facilitating receptivity by actions on cell membranes in the VTA if P has been applied to the hypothalamus 2 h earlier. Progesterone conjugated to BSA at carbon 11 (P-11-BSA) was ineffective compared to P-3-BSA using the same paradigm. This suggests that the mechanism which responds to P in the ventral midbrain may require the 11 region.