RATIONALE: Rat maternal behavior, which entails complex motivational and social factors, is disrupted by the currently available typical and atypical antipsychotics. It is thought that this disruption reflects a side effect of antipsychotics, modeling the neuroleptic-induced negative or deficit state. Amisulpiride and aripiprazole are new atypical antipsychotics with mechanisms of action distinct from the current typical and atypical antipsychotics. The effects of these drugs on maternal behavior have not been explored. OBJECTIVE: In the present study, we systematically examined the behavioral effects of amisulpiride and aripiprazole on maternal behavior in postpartum female rats. METHODS: Various components of maternal behavior (pup retrieval, pup licking, nest building and pup nursing) were examined repeatedly over a period of 24 h after a single injection of three doses of amisulpiride (10, 30, and 100 mg/kg s.c.) and aripiprazole (3, 10, and 30 mg/kg). RESULTS: Amisulpiride at the lower doses (10 and 30 mg/kg) enhanced pup licking, and only at the highest dose disrupted the active components of maternal behavior such as pup retrieval and nest building. Its effect was delayed in onset and prolonged as compared to other antipsychotics. Aripiprazole, even at the highest dose (30 mg/kg) did not impair pup retrieval or pup licking. However, it did disrupt nest building and led to enhanced pup nursing. CONCLUSIONS: The unique effects of these two drugs may be due to their unique actions at the mesolimbic dopamine synapses. The sparing of the major components of maternal behavior by aripiprazole may be related to its partial agonist effects, whereas the enhancement of pup licking by amisulpiride may be related to its dose-dependent preferential effect on the presynaptic autoreceptors. The potential clinical implications of these findings are discussed.