For therapeutic management of epileptic seizures in adults,second-generation antiepileptic drugs (AEDs) are better option than classical AEDs considering their safety concerns. Among these, Gabapentin (GBP) is most prescribed drug even during pregnancy. Reports on potential teratogenicity, developmental neurotoxicity and neurobehavioral alterations induced by in utero exposure to GBPare limited and inconclusive. Therefore, present study has been undertaken to evaluate the teratogenic safety, fetal neuro-toxicity; and its long-lasting functional impairments on young-adult rat offspring, if equivalent therapeutic doses of GBP were administered to pregnant rats. The pregnant C.F. rats were exposed to equivalent therapeutic doses of GBP at 300 and 400mg/kg BW/day from gestation day 0- 20. Half of the pregnant dams of both drug treated and control groups were sacrificed on GD 21, and fetuses were examined for gross congenital anomalies; then fetal brains were processed for histopathological observation, while remaining pregnant dams were allowed to deliver naturally and their pups were reared with their biological motherstill weaning,and independently up to PND 56 for neurobehavioural observations under selected mazes of anxiety and depression. There was dose-dependent significant reduction in body and brain weight of prenatally GBP treated rat fetuses. Histopathalogical observations showed substantial alterations in different neocortical layers of fetal brain.In utero GBP exposed rat offspring showed significantly increased state of anxiety like behavioural responses in open-field arena and on elevated plus-maze at PND 56. In behavioral despair maze,these rat offspring showed significant enhanced number of immobility phases (a depression sign). This study concludes that prenatal exposure toGBP during critical period of brain developmentmay induce fetal toxicity, neuroarchitectural changes and long-lasting impact on neurobehavioral alterations in young-adult offspring.
