Progestins and place preference conditioning after paced mating.

When female rats pace their coital interaction, a reward state evaluated by conditioned place preference is induced. Progesterone (P) is essential for the expression of proceptive behavior and for the induction of CPP. However, the functional significance of ring A reduction of P for the induction of this state during estrous is unsettled. In the present study, we evaluated whether ring A-reduced metabolites of P are involved in the reward state induced when the females are allowed to pace their sexual contacts. Ovariectomized (ovx) female rats treated with estradiol benzoate (EB, 5 microg) and P (13 microg), Megestrol acetate (MA; 13 microg ), 5 alpha-pregnan-20 dione (5 alphaDHP; 3 microg), or 5 beta-pregnan-3 alpha-ol-20-one (5 beta,3 alpha-Pgl; 3 microg) were used. Progestins were dissolved in propylene glycol and intravenously (iv) injected through an indwelling jugular catheter before females were tested for pacing behavior. After 15 intromissions or one ejaculation, females were gently placed in the nonpreferred compartment of a CPP box. Paced mating in all groups treated with progestins induced a clear change of preference. The administration of progestins alone did not induce CPP. These results suggest that P and ring A-reduced metabolites facilitate the reward state following pacing.

The nitric oxide pathway participates in estrous behavior induced by progesterone and some of its ring A-reduced metabolites.

Intracerebral and intravenous administration of progesterone (P) and its ring A-reduced metabolites induces intense sexual behavior (lordosis and proceptivity) in estrogen-primed rats. The present study tested the hypothesis that the nitric oxide-cGMP-protein kinase G pathway is involved in the facilitation of sexual behavior induced by the intracerebroventricular (i.c.v.) administration of P (130 ng) and its ring A-reduced metabolites 5alpha-dihydroprogesterone (5alpha-DHP; 13 ng) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl; 13 ng). In Experiment 1, we tested the relevance of the nitric oxide/cGMP pathway by infusing a nitric oxide synthase inhibitor or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor icv before progestin administration. The lordosis induced by P, 5alpha-DHP and 5alpha,3alpha-Pgl was significantly reduced at 2 h after progestin infusion by the previous injection of either a nitric oxide synthase inhibitor or by a soluble guanylyl cyclase inhibitor. Lordosis behavior returned to control values by 4 h. In Experiment 2, i.c.v. infusion of the protein kinase G inhibitor KT5823 significantly inhibited the lordosis behavior induced by all three progestins at 2 h. These data support the hypothesis that the nitric oxide/cGMP/protein kinase G pathway is involved in the lordosis induced by P and some of its ring A-reduced metabolites.