Effects of chronic administration of diphenylhydantoin on learning and offspring behavior.

An original parent group of 72 Sprague-Dawley albino rats was subdivided into four treatment groups that were administered 5, 10 or 15 mg/kg diphenylhydantoin and distilled water on days 5 to 55 after birth. At 85 days of age the drug females were bred to naive males to produce an F1 generation. In similar fashion, the F1 females were bred at maturity to produce and F2 generation. Neither offspring group received any drug administrations or experimental treatments. All three groups were tested on avoidance conditioning at 75 days of age for a total of 150 trials. The results of statistical analysis indicated no significant differences in number of correct responses in the parent group, a significant Drug effect in the offspring groups and a significant Dose effect in the F2 generation. This detrimental cross-generational effect on avoidance conditioning, caused by chronic diphenylhydantoin administration, is consistent with previously noted cross-generational effects of trifluoperazine, chlorpromazine, and methylphenidate.