Developmental, neuro and immunotoxic effects of perinatal diazepam treatment in rats

In utero exposure of rats to low dosages of diazepam (1.0 - 2.0 mg/kg) has been found to result in depression of the cellular and humoral immune respo nses during adulthood. Behavioral dysfunctions were also reported in infant s from mothers with high benzodiazepine (BDZ) intake during pregnancy. The present experiment was undertaken to reconsider the potential action of dia zepam during ontogeny in order to obtain further information about developm ental processes using a refined methodology. Time-pregnant rats were treate d subcutaneously with diazepam (2.0 mg/kg/day,: group E-1) or with diazepam vehicle (group C-1) from gestational day 14 to 20. Other dams (group E-2) received the same BDZ dose from the 1st to the 21st day of lactation (weani ng) or were not treated, remaining undisturbed in their home cages (group C -2). The following results were obtained for animals perinatally treated wi th diazepam compared to groups C-1 and C-2: 1-increased time for testis des cent and decreased time for vaginal opening (group E-2); 2 - no changes in the dates for ear end eye opening, or incisor tooth eruption (groups E-1 an d E-2); 3- increased locomotor activity in the open-field (group E-2) and/o r in the plus maze (groups E-1 and E-2); 4- decreased levels of anxiety mea sured in the plus maze (goups E-1 and E-2); 5- decreased macrophage spreadi ng and phagocytosis (groups E-1 and E-2) These results, which occurred in t he absence of overt signs of maternal or fetal toxicity, demonstrate develo pmental, neuro- and immunotoxic effects of perinatal diazepam treatment in rats.