Prenatal benzodiazepine effects in mice: postnatal behavioral development, response to drug challenges, and adult discrimination learning

Oxazepam treatment of primiparous mouse dams on days 12-16 of pregnancy (15 mg/kg p.o. twice daily) produced a transient retardation of postnatal body growth and neurobehavioral development, a reduction of the hyperactivity response to amphetamine in open-field tests on postnatal days 14-16, and a selective impairment of adult active avoidance in four go-no go discrimination tasks. Equally important for understanding the nature of the prenatal benzodiazepine syndrome were several negative results, namely, the absence of changes in homing performance on postnatal day 10, an intact hyperactivity response to scopolamine on postnatal days 21-23, a lack of effects on adult activity, and a normal passive avoidance performance in the go-no go tasks. A modification in monoaminergic regulatory functions may account for the overall profile of prenatal drug effects. Based on the results of this experiment, of a preliminary multidose study (0-50 mg/kg), and of an additional cross-fostering experiment, several methodological issues are addressed. These include the choice of appropriate treatment schedules and of testing procedures adequate for each developmental stage, and the control for various confounding variables such as litter effects, postnatal maternal influences, and developmental history.