Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research.
Diazepam was administered to gravid rat dams on days 13 through 20 of gestation, at either 1 or 5 mg/kg/day. Pups were observed on several behavioral paradigms throughout the preweaning period. The high dose resulted in a failure to maintain weight gain at the same rate as controls. Additionally, this dose produced a deficit in the ability of 8-day-old pups to autonomically thermoregulate. Female littermates of these pups displayed altered habituation behavior on a holeboard apparatus when tested on postnatal day 12 (PN 12). The low dose attenuated the normal drop in body temperature produced by removal of the pup from its home cage on PN8. This dose also slightly decreased responding on a photocell activity task on PN15. Neither dose was found to affect muscle strength, as measured by hang time. The results suggest that the postnatal effects of prenatal diazepam exposure are dose-specific, in that low dose treatment leads to a different type of behavioral consequence than does exposure to higher doses.