In utero exposure to atypical antipsychotic drug, risperidone: Effects on fetal neurotoxicity in hippocampal region and cognitive impairment in rat offspring

- Neurohistopathological study revealed substantial deficit in the thickness of hippocampal layers.
- EM study demonstrated apoptotic neurodegeneration in fetal hippocampus.
- Neurobehavioral study expressed cognitive impairment in young rat offspring.

Clinical studies indicate that about one-third of pregnant women with psychotic symptoms are exposed to either typical or atypical antipsychotic drugs (APDs). Reports on prenatal subject/model are lacking hence, the present study was undertaken to investigate the effect of prenatal exposure to risperidone (RIS) on the fetal hippocampus, and their related functional changes in young rat offspring. In this study, pregnant Wistar rats were exposed to equivalent therapeutic doses of RIS at 0.8 mg/kg, 1.0 mg/kg, and 2.0 mg/kg BW from gestation days (GD) 6 to 20. On GD 21, about half of the pregnant subjects of each group were euthanized, their fetuses were collected, fetal brains dissected, and processed for neurohistopathological evaluation. Remaining pregnant dams were allowed to deliver naturally and reared up to 8 weeks of age for neurobehavioral study under selected paradigms of cognition. Our results indicate that there was a significant decrease in the thickness of fetal hippocampus with the disturbed cytoarchitectural pattern, and volume of striatum and choroid plexus was also reduced. Furthermore, RIS treated young rat offspring displayed memory impairment on different mazes of learning and memory. The current study concludes that maternal exposure to clinically relevant doses of RIS may induce neurostructural changes in developing hippocampus and striatum, and cognitive sequelae in young offspring, respectively. Therefore, caution must be taken before prescribing this drug to pregnant subjects, especially during the sensitive phase of brain development. Hence, clinical correlation of animal data is urgently warranted.