Delayed development of reproductive functions and alteration of dopamine receptor binding in hypothalamus of rats exposed prenatally to phenytoin and phenobarbital.
Previous work in experimental animals treated prenatally with phenobarbital revealed reproductive changes in the offspring. Little has been reported on the effect of phenytoin or a combination of both drugs. 75 Pregnant Sprague-Dawley rats were administered either phenytoin (Na salt) at 20, 40 or 80 mg/kg orally (p.o.), phenobarbital (Na salt) at 20, 40 or 80 mg/kg subcutaneously (s.c.) or a combination of both drugs at the same doses daily from 5 to 20 days of pregnancy (4-12 rats/dose level). 24 Control rats received 1% methylcellulose p.o. and distilled water s.c. Regularity of estrous cycles was decreased in all treated groups, with the phenytoin group being most affected. The binding of [3H]spiroperidol, known to label dopamine receptors, was decreased in the hypothalamus of all drug-treated groups, indicating that the alteration in neuroendocrine function may be responsible for the above effects. Data suggest that prenatal exposure of rats to anticonvulsant drugs could lead to reproductive disorders.
D000818:Animals; D005260:Female; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D010634:Phenobarbital / Q000633:toxicity*; D010672:Phenytoin / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012098:Reproduction / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism
D011954:Receptors, Dopamine; D013134:Spiperone; D010672:Phenytoin; D010634:Phenobarbital