Central infusions of the recombinant human prolactin receptor antagonist, S179D-PRL, delay the onset of maternal behavior in steroid-primed, nulliparous female rats

The expression of maternal behavior in the newly parturient rat is under en docrine regulation. Blocking endogenous PRL secretion with bromocriptine de lays the normal rapid expression of maternal care shown toward foster young in steroid-primed virgin female rats. The recent development of the PRL re ceptor antagonist S179D-PRL, a mutant of human PRL in which the serine resi due at the 179 position is replaced with aspartate, provides a potentially useful tool to examine the role of PRL in neural processing. In the present report, three experiments were conducted that examined the effects of this PRL antagonist on the induction of maternal behavior. In each experiment, ovariectomized, nulliparous rats were treated sequentially with SILASTIC ca psules implanted sc with progesterone (days 1-11) and estradiol (days 11-17 ), a treatment that stimulates a rapid onset of maternal behavior in virgin rats. On day 11, females mere implanted with Alzet miniosmotic pumps conne cted to cannulae directed unilaterally at the lateral ventricle (Exp 1) or bilaterally at the medial preoptic area (MPOA; Exp 2 and 3). Pumps containe d either doses of S179D-PRL (0.115 or 1.15 mg/ml; Exp 1 and 2), wild-type h uman PRL (1.15 mg/ml; Exp 3), or the saline vehicle (Exp 1-3). Testing for maternal behavior began on day 12, a day after pump insertion, and animals were tested daily for 6 days. Latencies to contact, retrieve, and group fos ter test young were recorded. Administration of both the high and low doses of S179D-PRL infused into the lateral ventricle (Exp 1) or MPOA (Exp 2) si gnificantly delayed the onset of maternal behavior. In contrast, MPOA infus ions of the control hormone, wildtype human PRL, in Exp 3 did not delay the onset of maternal behavior. These findings support the concept that the ef fects of S179D-PRL are caused by its actions as a PRL receptor antagonist r ather than by a nonspecific effect of the protein. Overall, these results d emonstrate the effectiveness of S179D-PRL acting at the level of the centra l nervous system land, more specifically, within the MPOA) to regulate mate rnal behavior, a PRL-mediated response.