DEVELOPMENTAL AND BEHAVIORAL-EFFECTS OF PRENATAL PRIMIDONE EXPOSURE IN THE RAT

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0, 40, and 80 mg/kg. Althou gh these doses of PRM did not produce significant differences in litte r size, birth weight, mortality, date of attainment of developmental l andmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animal s approached and entered adulthood. When tested as adults, the 80 mg/k g male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and femal e PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its abil ity to produce lesions in the hippocampus and endocrine dysfunction re sulting in reproductive deficits. These results suggest that PRM produ ces its adverse effects as a result of its metabolism to phenobarbital , which in turn affects the limbic system. Copyright (C) 1996 Elsevier Science Inc.