Introduction: Drug-resistant epilepsy is an unmet medical condition that impacts 30% of epileptic patients. Numerous antiseizure drugs have already been developed but they provide only symptomatic relief and do not target the underlying pathogenesis. Preclinical models provide opportunities to gain insights into obscure mechanisms of drug-resistant epilepsy. Current animal models possess lacunae that need rectification and validation to discover novel antiepileptic drugs. The present study aims to validate 3 different doses of phenobarbital at 2 different periods.
Methods: Pentylenetetrazole was given at a sub-convulsive dose (30 mg/kg/day/intraperitoneal [IP]) for 28 days to develop kindling in male Wistar rats. Further, kindled rats were divided into the following four groups: Pentylenetetrazole control, pentylenetetrazole and phenobarbital (20 mg/kg), pentylenetetrazole and phenobarbital 40 mg/kg, and pentylenetetrazole and phenobarbital (60 mg/kg). They were assessed on days 14 and 28 post-kindling. Seizure scoring, oxidative stress, phenobarbital plasma levels, and histopathology of hippocampal neurons were analyzed.
Results: The results showed that the combination of pentylenetetrazole and phenobarbital (40 and 60 mg/kg) remarkably decreased seizure score, elucidated higher antioxidant effect, and prevented neuronal injury on day 14, whereas increased seizure score, oxidative stress, and neuronal death was observed with chronic administration of pentylenetetrazole and phenobarbital in kindled rats at day 28. Moreover, phenobarbital levels in blood were significantly increased at day 28 of phenobarbital treatment compared to day 14.
Conclusion: The adapted protocol with phenobarbital 40 mg/kg dose could be of great potential in screening antiseizure drugs in refractory epilepsy.

Introduction: Valproic acid (VPA) is the most widely used chemical to develop the preclinical model of autism spectrum disorder (ASD). However, in addition to inducing autism, it causes different teratogenic effects like teeth malformation, tail kink, and abnormal body growth in offspring. So far, no study has explored VPA-induced maternal misbehavior, miscarriage, and maternal cannibalism. We aimed to determine the cannibalistic effects of VPA in pregnant female Wistar rats and VPA’s influence on causing miscarriage frequency.
Methods: Our study was conducted on pregnant Wistar rats. On gestation day (GD) 12.5, they were treated with VPA (600 mg/kg intraperitoneal) dissolved in saline at 250 mg/mL concentration. The observations were mean litter size, mean male/female pups, mean mortality, maternal cannibalism, mean number of pups alive, cannibalism of malformed pups, miscarriage, survival analysis of pups, and odds and risk ratio were calculated for deaths observed in both study (control and VPA-treated) groups. The study was conducted till the weaning period. 
Results: VPA-exposed pregnant females portrayed significantly decreased litter size (P<0.0001), significantly higher cannibalistic behavior (P=0.0023), and significantly higher cannibalism of malformed pups (P=0.0484) than the control group. VPA had caused complete pregnancy loss (miscarriage) in 5 pregnant females. Moreover, the VPA group’s mortality percentage (P=0.0019) was significantly higher than the control group.
Conclusion: Overall, VPA has marked teratogenic effects (anatomical and morphological changes in offspring) with maternal behavior disruption, which causes cannibalism in Wistar female rats. The current manuscript findings can aid in investigating the novel mechanisms involved in maternal behavior disruption during the development of the VPA autism model.