Prenatal stress induces body weight deficit and behavioural alterations in rats: the effect of diazepam

Prenatal stress may induce intrauterine growth retardation, but it is not known whether a treatment with the anxiolytic benzodiazepine, diazepam may interfere with this phenomenon. A daily physical stress consisting of a forced immersion for 15 min in cold water was applied to pregnant rats of the Wistar strain from gestational day 5 until parturition. Animals were treated either with physiological saline or with diazepam (0.1 or 1 mg/kg/day) injected intraperitoneally 1 h prior to stress application. Control animals received injections of physiological saline but were not subjected to physical stress. Newborn pups subjected to prenatal stress showed reduced body weight as compared to control animals. Offspring were also examined for the appearance day of the following reflexes: cliff aversion, startle, righting, forelimb placing, forelimb grasping and bar holding. Hair growth, and first day of ears and eyes opening was also scored. At 60 days of age, male rats from the three experimental groups were subjected to behavioural tests, i.e., constrained swim (despair test) and step-through passive avoidance response. Animals subjected to prenatal stress showed a delayed appearance of all neonatal reflexes and behavioural deficits in adulthood, namely increased immobility in the despair test and reduced retention of a passive avoidance task. The prenatal treatment with diazepam totally counteracted the effect of stress, normalizing the time-course of neonatal reflexes and the behavioural responses in adulthood. No difference was seen between the effects of the two drug doses. It is concluded that prenatal physical stress may induce body growth retardation and may be considered as a model for human intrauterine growth retardation. The treatment with an anxiolytic benzodiazepine, such as diazepam, may counteract the effects of prenatal stress interfering with the biological consequences of stress concerning probably cerebral neurotransmitters in both the unborn foetus and the pregnant rat. (C) 1999 Elsevier Science BN. All rights reserved.