Adult virgin female rats display maternal behavior when continuously exposed to foster young for 5-6 days. Central infusions of PRL or placental lactogens (PLs) together with systemic treatment of progesterone (P) and estradiol (E2) stimulate maternal behavior in 1-2 days. In the present set of studies, it was asked whether the actions of lactogenic hormones are dependent upon both E2 and P and specific to lactogenic molecules. Moreover, we wanted to know whether central infusions of rat (r) PRL and PLs were equally effective in inducing maternal behavior. In the first study, adult virgin rats were ovariectomized (ovx) and stereotaxically fitted with bilateral cannulas directed at the medial preoptic area (MPOA). Rats were then assigned to one of four groups: P plus E2, blank (B) plus E2, P plus B, and B plus B. P-filled or B capsules were implanted sc on treatment day 1 and removed on day 11, whereas E2 or B capsules were implanted on day 11. All groups were infused with rPRL (40 ng/side) five times from days 11-13 and injected with bromocriptine (CB-154) sc (days 11-17) to suppress endogenous PRL release. Behavioral testing was conducted daily from days 12-17. It was found that exposure to both P and E2 was necessary to induce a fast onset of maternal behavior in PRL-infused females; priming with P or E2 alone in PRL-treated rats failed to stimulate a fast onset of behavior relative to that in nonsteroid-treated controls. In the second experiment to determine the biochemical specificity of PRL's action, adult nulliparous rats were ovx, implanted with bilateral cannulas directed at the MPOA, treated with both P and E2, injected with CB-154, and infused centrally (five times) with 40 ng (per side) of bovine GH, ovine LH, or vehicle. Central infusions of either bovine GH or ovine LH failed to stimulate maternal behavior, suggesting that the stimulatory actions of PRL are related to its lactogenic properties. In the final study, rats were ovx, fitted with bilateral cannulas directed at the MPOA; treated with P, E2, and CB-154; and given a single set of bilateral infusions of rPL-I or rPRL (40 ng/side.infusion) on day 11, three sets of infusions of rPL-I or rPRL (days 11 and 12), or vehicle infusions. Rats given three infusions of rPL-I and rPRL responded faster than controls, although the effect was not as robust as that in animals given five infusions in the initial study. rPL-I and rPRL groups did not differ from one another. Together these studies indicate that 1) both P and E2 are required for lactogenic stimulation of maternal behavior; 2) the stimulatory actions of PRL and rPLs on maternal behavior are related to their lactogenic properties; 3) extended treatment of females with lactogenic hormones is more effective in stimulating the onset of maternal behavior; and 4) the neural potencies of rPRL and rPL-I are similar. These findings provide support for the idea that the induction of maternal behavior is stimulated by the central actions of lactogenic hormones.

The present study examined possible changes in the dopaminergic regulation of prolactin (PRL) secretion which have been reported to occur in reproductively experienced female rats. In the first experiment, female rats which had raised a litter to weaning and age-matched nulliparous controls were ovariectomized and challenged sequentially 2 days apart with a low (0.2 mg/kg) and high (1.0 mg/kg) dose (intravenously) of haloperidol (HAL), a dopamine antagonist. Blood samples were collected via intra-atrial catheters, and plasma samples were assayed for PRL content by radioimmunoassay. Whereas HAL stimulated increases in plasma PRL concentrations in both nulliparous and primiparous animals, significantly higher levels of plasma PRL were present after both doses of HAL in the nulliparous rats. A second experiment investigated the role of lactation in this change in the ability of HAL to stimulate increases in circulating PRL levels. Separate sets of age-matched primiparous (pups removed on day 1 of lactation) and nulliparous rats were challenged with two doses of HAL 2 weeks after gonadectomy. In contrast to the effect of pregnancy and lactation found in the first experiment, pregnancy and parturition in the absence of lactation failed to alter the female’s sensitivity to HAL. The PRL responses in the two groups were identical at the low HAL dose and similar after the high HAL dose. These findings demonstrate that a single prior pregnancy and lactation, but not pregnancy alone, significantly reduce the ability of HAL to elevate circulating plasma PRL concentrations. Decreased circulating PRL levels in reproductively experienced females, therefore, may result in part from increased endogenous dopaminergic activity/tone.