Haloperidol and clozapine affect social behaviour in rats postnatally lesioned in the ventral hippocampus

Neonatal ibotenic acid lesion of the ventral hippocampus results in altered patterns of social behaviour. After puberty, lesioned animals spent less time in social interaction and the nonaggressive/aggressive behaviour ratio shifted towards increased aggressiveness. In this study, the effects on social behaviour of the neuroleptic drugs haloperidol (HAL) and clozapine (CLO) after acute and subchronic treatment were studied. Seven-day-old rats were lesioned and social behaviour was tested at the age of 13 weeks. Drug effects were tested after acute (HAL 0.025 mg/kg, CLO 1.0 mg/kg) and subchronic (10 injections, HAL 0.075 mg/kg, CLO 5.0 mg/kg) administration. For comparison, diazepam (DZP, 0.5 mg/kg) was used in the acute experiment. After acute administration, DZP had no effect on social behaviour in sham-lesioned rats, but nonaggressive behaviour increased significantly in lesioned animals. CLO and HAL did reduce the time sham-lesioned rats spent in social contact, and CLO also increased % nonaggressive behaviour in lesioned rats. Here, HAL had no effect. Subchronic administration did not alter social behaviour in sham-lesioned animals. However, CLO increased the time lesioned animals spent in social interaction, whereas HAL had an effect on nonaggressive behaviour. The results of this study indicate that the lesion model is sensitive to differentiated effects of classical neuroleptic drugs such as HAL and atypical neuroleptic drugs like CLO. It might be a useful tool in the search for potential neuroleptic drugs.