Abstract
Objective: Psychiatric disorders are relatively common among women of childbearing age. However, the use of antipsychotics during pregnancy remains controversial. Previous animal studies indicate that prenatal exposure to antipsychotics may impair the cognitive function of adult offspring. The current study investigated whether prenatal risperidone treatment would produce long-term effects on behavior in adult male offspring.
Methods: All plug-positive female C57BL/6 mice were randomized two groups. Pregnant dams of both groups received a daily intraperitoneal injection of risperidone (2mg/kg body weight) or vehicle from embryonic day 6 to 16. Pups were reared by their biological mothers. Experiment 1 examined the short-term effects of prenatal risperidone on hippocampal synaptic protein expression levels of the male pups on P10. In experiment 2, mice were examined in the spontaneous locomotion, spatial object recognition, elevated plus maze and prepulse inhibition of acoustic startle reflex sequentially on P75.
Results: The data showed no significant difference in the body weight of treated offspring as compared to those of the controls. The postsynaptic protein PSD-95 in the hippocampus of male pups was downregulated by prenatal risperidone exposure. The total distance traveled in the novel environment of the open field test did not reveal any differences between two groups. Male mice offspring exposed to risperidone showed deficits in novel object recognition when compared with control group. Prenatal risperidone treatment has no significant effects on anxiety-related behavior in adult male offspring. However, the offspring of risperidone group showed significantly potentiated PPI.
Conclusion: Prenatal exposure to risperidone during a critical period of brain development leaves a lasting imprint on the brain. The findings of impaired recognition memory, reduced synaptic molecules of hippocampus, and enhanced prepulse inhibition suggest that prenatal risperidone could produce both negative and possible positive effects. The mechanism of risperidone’s action on neurodevelopment remains to be clarified.