Rats were subjected to restraint stress for nine hours daily, on three consecutive days, at various stages of pregnancy from days 9–20, and the postnatal development and behaviour of the offspring assessed on a wide‐ranging battery of tests. Stress at any of the stages of pregnancy investigated caused a significant decrease in offspring body weight persisting up to 6 weeks of age, and delayed the appearance of certain developmental landmarks such as ear opening, auditory startle and cliff avoidance responses. Postnatal mortality and impairment of ability to orient to the home cage were also significantly increased in the offspring from rats stressed on days 18–20 of pregnancy. In a second experiment, the effects of restraint stress on days 18–20 were investigated in more detail. At birth, stressed and control offspring were fostered onto mothers from the same treatment group or cross‐fostered onto mothers from the opposite treatment group and assessed as before, to determine whether the adverse effects observed in the first experiment were prenatally or postnatally mediated. The effects were most marked in prenatally stressed pups reared by stressed mothers and least marked in controls reared by controls, with the other two cross‐fostered groups being intermediate; this indicates that the effects were induced partly prenatally at the time of treatment and partly postnatally by the rearing mothers that had been stressed.

The effect of daily, oral administration of diazepam on plasma corticosterone responses to stressors of varying intensity was investigated. In rats exposed to the mild stress of noise, diazepam, 10 mg kg-1 but not 1.0 or 0.1 mg kg-1, reduced plasma corticosterone concentrations by 30% in comparison with controls. However, in rats exposed to the more severe stressors, foot-shock or immobilization, none of these doses of diazepam reduced plasma corticosterone responses. In unstressed rats, diazepam 10 mg kg-1 raised plasma corticosterone concentrations. It is suggested that plasma corticosterone concentrations are not a reliable indicator of the tranquillizing effect of diazepam during stress.

The aims of the experiments were to investigate the effects of diazepam treatment on day 14 of pregnancy in the mouse on endogenous maternal plasma corticosterone levels and induction of cleft palate (CP) in the offspring, and to evaluate any interaction between diazepam and stress‐induced or corticosterone‐induced CP. Sub‐teratogenic doses of diazepam (10 mg/kg orally, given t ice 12h apart) had no significant effect on the induction of CP by 24h maternal food deprivation. Similarly, neither sub‐teratogenic doses (10 or 50 mg/kg, given twice) nor teratogenic doses (100 mg/kg, given twice) of diazepam had any significant effect on the induction of CP by exogenous corticosterone given at low (2.5 mg) or high (10 mg) doses. However, diazepam alone (10‐400 mg/kg) raised endogenous plasma corticosterone levels in a dose‐related way. Mice given teratogenic doses of diazepam, 100 or 200 mg/kg, causing 3‐6% CP, sustained elevated endogenous corticosterone levels for at least 6h after dosing, in comparison with sub‐teratogenic doses of diazepam or vehicle controls. In a comparison of mice given 400 mg/kg diazepam, causing 20% CP, with mice given 2.5 mg corticosterone, causing 25% CP, the mean endogenous corticosterone level was lower in the diazepam group at 1h but higher at 6h after dosing than that of the exogenous corticosterone group. These results suggest that diazepam may cause CP in the mouse by raising endogenous maternal corticosterone levels. The stress of fasting and immobilisation resulting from the heavy sedation caused by teratogenic doses of diazepam may contribute to the elevations in endogenous corticosterone levels.

Rats on days 12--14 of pregnancy were treated with restraint stress alone (9h daily), restraint stress plus diazepam (1 mg/kg, twice daily), diazepam alone, or left as untreated controls. Postnatal development and behaviour was assessed on a wide-ranging battery of tests. Offspring of mothers subjected to restraint stress alone were significantly retarded on a number of developmental measures including growth, ear-opening, cliff avoidance response, auditory startle response and mid-air righting reflex. When adult these offspring also showed significantly impaired learning ability in a swimming maze. However, the rate of development and learning ability in the restraint plus diazepam or diazepam alone groups was comparable to or slightly advanced of that in untreated controls. It is concluded that concurrent administration of a low dose of the tranquiliser diazepam during restraint stress prevents the adverse postnatal effects of maternal restraint stress.

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