Developmental alterations in maturing rats caused by chronic prenatal and postnatal diazepam treatments

The post treatment effects of early prenatal, late prenatal, early postnatal or combined prenatal and neonatal treatment with diazepam on the development of pain sensitivity, acoustic startle responsiveness, and benzodiazepine receptors in the cerebral cortex were investigated in rats between 14 and 90 days of age. Tail-flick latency was significantly decreased by combined prenatal and neonatal and by early prenatal diazepam treatment, but not by diazepam during the last half of gestation or during the neonatal period alone. Acoustic startle response was decreased by either late prenatal or neonatal diazepam treatment, but not by early prenatal treatment alone. Density of benzodiazepine receptors in the cortex was increased from postnatal day 1 to 21 by either early or late prenatal diazepam treatment. Neonatal diazepam treatment suppressed cortical benzodiazepine receptor or development until postnatal day 21; thereafter, receptor density increased to significantly higher values than in controls at 90 days of age. The results demonstrate that diazepam can alter development of pain sensitivity by actions during early gestation, startle responsiveness by actions late in pregnancy, and cortical benzodiazepine receptors by actions throughout gestation and the early postnatal period.