Effects of prenatal diphenylhydantoin treatment on reproductive outcome, development, and behavior in rats.
Pregnant Sprague-Dawley rats were administered sodium diphenylhydantoin (DPH) by gavage on gestation days 9-18 in doses of 0, 100, or 200 mg/kg. DPH-treated dams showed a dose-related decrease in weight gain throughout the drug treatment period. Offspring had significantly lowered birth weights, along with increased mortality through the first 30 days of life. In one of the experiments specifically designed to measure pup mortality, the rates were 41.4% and 60.7% respectively, for the 100 and 200 mg/kg DPH groups. Shortly after eye opening, many of the DPH-treated animals developed chromodacryorrhea, a condition that remained throughout the experiment. Aside from lowered body weights, no differences were observed in the attainment of several standard developmental landmarks. During the neonatal period, the pups exposed in utero to 100 mg/kg DPH showed a significant increase in pivoting locomotion on postnatal days 7 and 9. As adults, the animals exposed to 200 mg/kg DPH showed significant increases in locomotor activity measures. Both DPH groups developed a dose-related and highly abnormal spontaneous circling behavior. These results confirm a small but growing body of literature that demonstrates that DPH is a behavioral teratogen.
Pizzi
W J
WJ
Department of Psychology, Northeastern Illinois University, Chicago 60625.
Jersey
R M
RM
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D009043:Motor Activity / Q000187:drug effects*; D010672:Phenytoin / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D012727:Sex Characteristics; D013239:Stereotyped Behavior; D013723:Teratogens / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D013723:Teratogens; D010672:Phenytoin; D003913:Dextroamphetamine