Early postnatal exposure of rats to lamotrigine, but not phenytoin, reduces seizure threshold in adulthood

In view of previous reports of changes in seizure susceptibility in adult rats exposed to phenobarbital or diazepam as pups, we examined the effects of early life exposure to lamotrigine and phenytoin, two commonly used antiepileptic drugs (AEDs), for their effect on seizure threshold in adult rats. We found that pups exposed to lamotrigine for 6 days during the second postnatal week had a significantly lower threshold for pentylenetetrazole-evoked seizures when tested as adults. In contrast, phenytoin exposure during the second postnatal week was without a significant effect on seizure threshold in adults. Seizure scores at threshold were comparable across all groups tested. The dose of lamotrigine used in our study (20 mg/kg) was below that required to cause developmental neuronal apoptosis, whereas the dose of phenytoin used (50 mg/kg) was above that required for developmental neurotoxicity. Therefore, our findings suggest that neurodevelopmental alterations in seizure susceptibility may occur via mechanisms that are independent of those responsible for neural injury or teratogenesis. Our findings support the possibility that therapy with certain AEDs during pregnancy or infancy may alter seizure susceptibility later in life, a possibility that should be taken into account when examining early life factors that contribute to seizure susceptibility in adulthood.