Neutralization of pregnancy-preventing activity of cabergoline, a dopamine agonist with progesterone

Cabergoline (Cab), a dopamine agonist, inhibits the production and/or release of prolactin and reduces progesterone biosynthesis. Cab at doses of 20 microg/kg/d and higher administered on Days 1, 2 and 3 of pregnancy prevented implantation of fertilized ova in all treated female rats. The pregnancy-preventing activity of Cab is attributed to a deficiency of progesterone since estradiol levels remain unchanged. To validate the hypothesis that progesterone deficiency is the cause of the infertility, exogenous progesterone was administered to Cab-treated pregnant female rats and their fertility assessed. Progesterone at a dose of 5 mg/kg/d sc was administered on Days 1 to 7 of pregnancy to female rats treated with Cab (20 and 60 microg/kg/d) on Days 1, 2 and 3 of pregnancy. All progesterone-treated animals became pregnant, and all mated female rats treated with Cab (60 microg/kg/d) and progesterone (5 mg/kg/d) on Days 1 to 7 inclusive became pregnant. In conclusion, progesterone can neutralize the pregnancy preventing activity of Cab. Pregnant female rats treated with Cab can be used to assay for progestagenic activity of compounds.