Distinct neurobehavioral consequences of prenatal exposure to sulpiride (SUL) and risperidone (RIS) in rats

Antipsychotic treatment during pregnancy is indicated when risk of drug exposure to the fetus is outweighed by the untreated psychosis in the mother. Although increased risk of congenital malformation has not been associated with most available antipsychotic drugs, there is a paucity of knowledge on the subtle neurodevelopmental and behavioral consequences of prenatal receptor blockade by these drugs. In the present study, antipsychotic drugs, sulpiride (SUL, a selective D2 receptor antagonist) and risperidone (RIS, a D2/5HT2 receptor antagonist) were administered to pregnant Sprague–Dawley dams from gestational day 6 to 18. Both RIS and SUL prenatal exposed rats had lower birth body weights compared to controls. RIS exposure had a significant main effect to retard body weight growth in male offspring until postnatal day (PND) 60. Importantly, water maze tests revealed that SUL prenatal exposure impaired visual cue response in visual task performance (stimulus–response, S–R memory), but not place response as reflected in hidden platform task (spatial memory acquisition and retention). In addition, prenatal SUL treatment reduced spontaneous activity as measured in open field. Both behavioral deficits suggest that SUL prenatal exposure may lead to subtle disruption of striatum development and related learning and motor systems. RIS exposure failed to elicit deficits in both water maze tasks and increased rearing in open field test. These results suggest prenatal exposure to SUL and RIS may produce lasting effects on growth, locomotion and memory in rat offspring. And the differences may exist in the effects of antipsychotic drugs which selectively block dopamine D2 receptors (SUL) as compared to second generation drugs (RIS) that potently antagonize serotonin and dopamine receptors.