Intravenous progesterone elicits a more rapid induction of lordosis in rats than does SKF38393

In ovariectomized (ovx), estradiol (E)-primed rats, progesterone (P) facilitates sexual receptivity within 2–30 min following intravenous (i.v.) administration. Intracerebroventricular infusion of P or the dopamine receptor type 1-like (D1) agonist, SKF38393, increases lordosis in ovx, E-primed rats, and intracellular progestin receptor (PR) blockers attenuate P and SKF38393’s facilitation of lordosis. The present experiments examined whether P can have effects via Dl receptors and compared the onset of P’s and SKF38393’s induction of lordosis following i.v. administration. Ovx rats (N = 20) with i.v. jugular catheters were primed daily with 2 µg E subcutaneously and were pretested for sexual receptivity. In Experiment 1, rats (n = 10) were repeatedly tested for receptivity 3–7, 15, 30, 60, and 120 min following i.v. infusion of P (2 µg), SKF38393 (100 ng), and propylene glycol vehicle (0.2 cc). Progesterone increased postinfusion lordosis at all test times, whereas SKF38393’s increases in lordosis were not statistically significant until 15 min following i.v. infusion, relative to lordosis following vehicle or pretest conditions in Experiment 1. In Experiment 2, rats (n = 15; 5 from Experiment 1, and 10 new subjects) received infusions of the antiprogestin, RU38486, the D1 antagonist, SCH23390, or vehicle followed by a second P or vehicle infusion. Although both RU38486 and SCH23390 blocked the facilitatory effects of P on lordosis, their effects varied. RU38486 completely blocked P’s effects, whereas SCH23390 did not. In Experiment 3, rats (n = 15, from Experiment 2) received infusions of RU38486, SCH23390, or vehicle followed by a second SKF38393 or vehicle infusion. RU38486 and SCH23390 both effectively blocked the facilitatory effects of SKF38393 on lordosis. In Experiment 4, rats (n = 15, from Experiment 3) received i.v. infusions of P, which rapidly and significantly increased the number of super-threshold spikes in the ventral tegmental area, but not in the ventral medial hypothalamus or in the parietal cortex. These data suggest that actions at intracellular progestin receptors do not account for all of P’s effects to facilitate receptivity. Interestingly, although PRs may be involved in P and D1 ligand’s activation of female sexual behavior, D1 receptors are not required for P’s effects. However, i.v. P rapidly and significantly alters neuronal activity in sites with the greatest concentration of dopamine neurons (ventral tegmental area > ventral medial hypothalamus > cortex).