Prevention and termination of pregnancy in rats by cabergoline, a dopamine agonist.
The objective of the study was to clarify the potency and action of cabergoline, a dopamine agonist, in preventing and terminating pregnancy in rats. Cabergoline administered s.c. to female rats on days 1, 2 and 3 of pregnancy prevented implantation of the fertilized ova and development of the embryos. The drug was 100% effective at doses of 10 micrograms kg-1 day-1 or higher. Serum progesterone determined on day 8 of pregnancy was significantly reduced in rats treated with cabergoline at doses of 5 micrograms kg-1 day-1 and higher, whereas serum concentrations of oestradiol remained unchanged. Cabergoline at doses of 10 and 20 micrograms kg-1 day-1 administered s.c. on days 7, 8 and 9 of pregnancy was partially effective (43 and 50%, respectively) in terminating pregnancy, whereas at doses of 30 micrograms kg-1 day-1, and higher, pregnancy was terminated in all treated rats. Serum concentrations of progesterone on days 12 and 16 of pregnancy were significantly lower in rats treated with doses of 10 micrograms kg-1 day-1 or higher. Serum prolactin determined on day 4 of pregnancy in rats treated with cabergoline at the effective dose of 10 micrograms kg-1 day-1 on days 1, 2 and 3 of pregnancy was significantly reduced to 1.7 +/- 0.62 ng ml-1 from a pretreatment value of 16.0 ng ml-1. The lowest effective dose of cabergoline in reducing serum prolactin determined on day 8 of pregnancy was 20 micrograms kg-1 day-1. The present results support the hypothesis that cabergoline acts by inhibiting prolactin production or release, thereby inhibiting progesterone biosynthesis by the ovary.
Negishi
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Department of Obstetrics and Gynecology, Hokkaido University, School of Medicine, Sapporo, Japan.
Koide
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D000818:Animals; D000077465:Cabergoline; D003271:Contraceptive Agents, Female; D018491:Dopamine Agonists / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects*; D004873:Ergolines / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D005260:Female; D008297:Male; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D003271:Contraceptive Agents, Female; D018491:Dopamine Agonists; D004873:Ergolines; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D000077465:Cabergoline