Neuroarchitectural Disturbances In Fetal Hippocampus And Neurofunctional Impairment In Young Rats Prenatally Exposed To Antiepileptic Gabapentin

Research Article
Singh K.P and Kiran Gupta
Antiepileptic drugs, gabapentin, valproic acid, cognition, prenatal, rat

Antiepileptic drugs are used to treat seizures in pregnant women may cause cognitive impairment in children. It is still unknown whether in utero exposure to gabapentin (GBP) may induce neuropathological changes in fetal brain, and related functional disturbances in adolescents. Therefore, present study has been designed to evaluate the effects of prenatal exposure to GBP on neurostructural changes in fetal hippocampus; and their long-lasting impact on cognitive performance in young rat offspring; and to compare these findings with a classical drug, valproic acid (VPA) for drug safety concern. The nulliparous pregnant rats were exposed to GBP (300 and 400mg) and VPA (50,100 and 200mg) from gestation day (GD) 0-20. On GD 21, about half of the pregnant rats of all groups were sacrificed; their fetal brains were processed for paraffin microtomy of hippocampal area. Remaining drug treated and control dams were allowed to deliver naturally, and pups were reared with their biological mothers up to postnatal day (PND) 21. At 8 weeks of age, offspring were subjected to test of cognition (T- maze). Neurohistopathological evaluation of GBP and VPA exposed fetal brains revealed that laminar architecture of typical three layered hippocampal cortex was found to be less developed, poorly differentiated and substantially reduced in size in comparison to vehicle treated group. Further, prenatally drug treated young offspring displayed cognitive impairment performance in T maze. These findings suggest that prenatal exposure to GBP or VPA during organogenesis showed not only neuroarchitectural alterations but also induced long-lasting impact on cognitive performance in young offspring