Progesterone receptor activation signals behavioral transitions across the reproductive cycle of the female rabbit

The female rabbit is an exceptional experimental model to define mechanisms by which progesterone (P) controls the expression of reproductive behaviors. In the rabbit, the rise in P levels during pregnancy inhibits estrous scent marking ("chinning"), stimulates the excavation of a nest burrow ("digging"), and primes behaviors later used for nest construction. The pre-parturient fall of P triggers the construction of a straw nest ("straw carrying") that is lined with hair that she pulls from her own body ("hair pulling"). These behaviors can be replicated in ovariectomized (ovx) females given a schedule of estradiol (E) and P that mimics hormone levels during pregnancy (E from days 0 to 4, E + P from days 5 to 17, E from days 18 to 27). We administered PR antagonists RU486 or CDB(VA)2914 to ovx female rabbits during either the initial (days 5-11) or late (days 12-17) phases of P treatment, to determine the role of PR activation in coordinating the expression of these behaviors. Both antiprogestins attenuated the P-mediated decline in chinning and increase in digging when administered during days 5-11. When given across days 12-17, both antiprogestins triggered an early decline in digging, the onset of nest building in some Ss, and the reinstatement of chinning. These results point to a central role of PR activation for establishing and maintaining the behavioral phenotype of pregnancy, and for the behavioral transition from pregnancy to estrus.