Behavioral changes persisting into adulthood after neonatal benzodiazepine administration in the rat.

Abstract

The day after birth male pups of hooded Lister rats were randomly fostered to form experimental litters of eight. Within each litter pups were randomly assigned among the following groups: vehicle control; diazepam (1, 5 or 10 mg/kg); lorazepam (0.25, 0.5, 1 or 2.5 mg/kg). Injections were given daily from day 1 until weaning at day 21. The pups were then tested as adults, from day 65. There were no effects of neonatal treatment when the pups were tested undrugged in 3 animal tests of anxiety, but in the social interaction test the neonatal diazepam treatment significantly reduced the anxiogenic effects of yohimbine. The neonatal diazepam treatment significantly enhanced the sedative effects of a challenge dose of chlordiazepoxide in the holeboard. Passive avoidance acquisition and retention were unaffected by the early treatment. Neonatal treatment with both benzodiazepines reduced the incidence of myoclonic jerks when the pups were challenged with pentylenetetrazole. Both neonatal treatments enhanced aggressive acts displayed when the residents were confronted with an intruder in their home-cages. However, when the rats that had been treated neonatally with lorazepam were themselves intruding into another's territory, they were significantly more submissive.