Effect of Restraint Stress during Gestation on Pentylenetetrazol-Induced Epileptic Behaviors in Rat Offspring

Objective(s): Epilepsy is a neurodevelopmental disorder which is strongly influenced by genetic and environmental factors. Gestational stress has been shown to be an important factor for affecting seizure susceptibility. The present study was conducted to address whether gestational stress may affect pentylentetrazol (PTZ)-induced epileptic behavior in rat offspring in a sex- and age- dependent manner. Materials and Methods: Pregnant rats were divided into control and stressed groups (n=6 in each). In the stressed group, pregnant rats were under restraint stress and held immobile in the Plexiglas tube twice per day one hour per session for three consecutive days started on day 17 of pregnancy. To induce seizure, on postnatal days 15 (P15) and 25 (P25), PTZ (40-50 mg/kg, IP) was injected to rat offspring (n=12, one male and one female from any litter for each group/day). Then, epileptic behaviors of each rat were recorded. Results: Epileptic behaviors of stressed pups showed significant changes in comparison to control ones. The time to onset of the first epileptic behavior was shortened while mean duration and frequency of tonic-clonic attacks increased in stressed pups on both P15 and P25. Female offspring were different from male offspring in terms of epileptic behavior. Moreover, focal attacks were more obvious and significantly longer in the offspring of stressed group at the age of 25 days than those of 15 day old. Conclusion: Prenatal restraint stress potentiated PTZ-induced epileptic behavior, age and sex dependently, probably due to alteration of neural and endocrine pathways during developmental process. Male and younger rats were more sensitive to stress than female and older ones.