Diazepam effects on the fetus

Treatment of time-pregnant Long Evans rats with 1.25 mg/kg s.c. diazepam (2.5 mg/kg in Sprague Dawley rats) from gestational day 14 to 20 produced transient depression of an olfactory guided behavior (nest odor behavior) in suckling offspring. Enhanced drug sensitivity to diazepam was seen in adult male and female off-spring as indicated by increased temperature depression. In addition, increased sensitivity to an opiate (morphine) was noted for the female offspring in the tail flick test. Treatment of the pregnant dam with diazepam or clonazepam, a benzodiazepine with selective affinity for the central benzodiazepine receptor, resulted in a marked depression of cellular immune responses in the offspring of both sexes up to 2 months of age. Drug treatment during early fetal period (GD 12-16), at a time central benzodiazepine receptors are not present in all brain regions of the fetal brain, did not affect the quality of cellular immune responses, whereas treatment from GD 16 to 20 was effective. Prenatal diazepam effects are discussed in view of presence and functionality of both central and peripheral benzodiazepine binding sites in the fetus.