Effects of chronic typical and atypical antipsychotic drug treatment on maternal behavior in rats

Understanding the effects of antipsychotics on maternal behavior is important for understanding the poor quality of mother-infant interaction in schizophrenia. Previous preclinical work has demonstrated that acute treatment with typical and atypical antipsychotics disrupts maternal behavior. However, the effects of chronic antipsychotic treatment on maternal behavior are unknown. This issue is of importance since clinical use of antipsychotic medication requires continuous exposure to these drugs. In this study, we treated postpartum rats with haloperidol (0.25 mg/kg/day) or olanzapine (7.5 mg/kg/day), via osmotic minipumps or daily injections for 3 weeks. Maternal behavior was assessed every third day. On each observation day, maternal behavior was observed twice, once just prior to the daily injection (“trough” as this was 24 h after last injection) and again 2 h after the injection (“peak”). Daily injections of haloperidol and olanzapine significantly disrupted pup retrieval, pup licking, nest building at peak, but this effect was gone by trough. Drug administration via minipumps also disrupted these behaviors, but the effects were less severe. Pup nursing was enhanced by either method of drug administration. No evidence of sensitization or tolerance associated with chronic drug treatment was found. It is concluded that chronic antipsychotic treatment disrupts active maternal behaviors and this disruption, most likely to lead to side effects in humans, should be avoided in future drug development.