Short-, medium-, and long-term effects of prenatal oxazepam on neurobehavioural development of mice

Abstract

A benzodiazepine (oxazepam) was given to nulliparous mice on days 12–16 of pregnancy, and the development and young adult behaviour of the offspring were studied. Experiment 1, using 5, 15, and 50 mg/kg doses given PO twice daily, showed a dose-dependent retardation of postnatal development of several responses such as righting, bar holding, limb placing, and auditory startle. These changes were maximal in the first 2 postnatal weeks and then were markedly attenuated, or disappeared, being apparently related to a temporary retardation of body growth. A reduction of locomotor activity at 60 days was found only in the 50 mg/kg group. The effects of the 15 mg/kg dose on postnatal body growth and neurobehavioural development were replicated in Experiments 2 and 3. Moreover, in these experiments prenatal oxazepam reduced open field activity at 14–16 days and attenuated the hyperactivity induced by dl-amphetamine sulphate (2 mg/kg IP). On the other hand activity, habituation, and response to a scopolamine challenge (2 mg/kg IP) at 21–23 days were not significantly different from those of appropriate controls. Experiment 3, using a cross-fostering procedure, showed that postnatal maternal effects were not responsible for the changes so far mentioned. Experiment 2 also investigated the acquisition of several go-no go avoidance discriminations in a shuttle-box, using either light (L) or buzzer noise (N) as the “go” signal, a compound “no go” signal (NL in the L-“go” groups and LN in the N-“go” groups), and either an extinction or a passive avoidance contingency during the “no go” signal (4 weeks of training, starting at 60 days). The main effect of prenatal oxazepam was an impairment of active avoidance responding, while the treatment effects on overall discrimination performance were less marked and limited to the later stages of training.