The effects of neonatal administration of clonazepam on passive avoidance and on social, aggressive and exploratory behavior of adolescent male rats.

Abstract

Male offspring of hooded Lister rats were fostered at birth to form experimental litters of eight. Within each litter pups were randomly allocated among drug groups. Administration of clonazepam (1-5 mg/kg/day) to pups from neonatal days 1-21 resulted in high mortality, at least partly due to impaired ultrasonic calling. Pups treated with 0.1, 0.5 or 1 mg/kg/day throughout the preweaning period were then tested undrugged during adolescence to assess any lasting behavioral changes. There were no significant changes in the social interaction test or in the acquisition or retention of a passive avoidance task. However, neonatal treatment with clonazepam (0.1 mg/kg) did produce significantly less exploratory head-dipping and locomotor activity in a holeboard. This dose also enhanced offensive behaviors when rats were resident in their home-cages and confronted with an intruder, but increased submissive behaviors when the treated rats were intruding into another rat's territory. Treatment with higher doses of clonazepam (0.5 and 1 mg/kg) produced more dominance behaviors when the pups were intruders. Since the main behavioral changes were found in the lowest dose group, which did not show any weight loss, they are unlikely to be secondary to changes in the risk of mortality.