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Effects of prenatal diphenylhydantoin treatment on reproductive outcome, development, and behavior in rats
1Department of Psychology, Northeastern Illinois University, Chicago 60625.
Insights
Sodium diphenylhydantoin (DPH) exposure during pregnancy in rats caused decreased maternal weight gain, increased offspring mortality, and abnormal behaviors like circling. These findings indicate DPH is a behavioral teratogen.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Sodium diphenylhydantoin (DPH) is an anticonvulsant medication.
- Previous research suggests potential developmental effects of DPH.
Purpose of the Study:
- To investigate the developmental and behavioral effects of prenatal sodium diphenylhydantoin (DPH) exposure in Sprague-Dawley rats.
Main Methods:
- Pregnant rats received DPH (0, 100, or 200 mg/kg) via gavage during gestation days 9-18.
- Offspring were monitored for birth weight, mortality, developmental landmarks, and behavioral changes.
Main Results:
- DPH caused dose-related decreases in maternal weight gain and significantly lowered offspring birth weights.
- Increased offspring mortality and the development of chromodacryorrhea were observed.
- Prenatal DPH exposure led to abnormal behaviors, including increased pivoting locomotion and spontaneous circling in offspring.
Conclusions:
- DPH is a behavioral teratogen, inducing significant developmental and behavioral abnormalities in offspring.
- The study confirms and expands upon existing literature regarding DPH's teratogenic potential.
Abstract:
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.