Abstracts

Antiepileptic drugs (ADs), used to treat seizures in children, can cause cognitive impairment, possibly due to a pro-apoptotic effect of ADs that coincides with a critical growth spurt period. In adult rats, pretreatment with certain novel ADs is ineffective at blocking seizures; however some afford neuroprotection. Potential side-effects of chronic AD treatment in development are unknown. Therefore, we tested the effects of novel antiepileptic drugs on growth and mortality, seizure severity, and cognition in the presence and absence of kainate (KA)-induced status epilepticus during the 2nd-3rd postnatal (P) weeks of rat development. Lamotrigine (LTG), carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA) (5-50 mg/kg) were first administered (i.p.) on P14 and then continued daily for 7 days before status epilepticus was induced with KA on P21. Animals were weighed each day just prior to AD treatments. Seizure severity was quantified from the electroencephalograph (EEG). Memory impairment was tested in the Morris Water Maze after a 2 day rest and continued AD treatment. Chronic treatment with any of the four ADs tested was ineffective in preventing KA-induced EEG ictal activity. However, 5 days of LTG treatment, caused rat pups to be smaller in size and weight than vehicle injected controls (44.5g. increase vs. 66.0 g). LTG groups appeared to develop tolerance as the weight difference was not significant at the end of the experiment. LTG, VPA, and CBZ did not affect mortality, but PHT increased mortality identifying a critical detrimental side-effect of this drug. Chronic LTG, VPA, and PHT in the absence of KA did not affect learning and memory, but CBZ diminished performance in the Morris Water Maze (C: 16.6s v. CBZ: 34.6s per trial). CBZ and PHT did not prevent KA-induced learning deficits, but LTG- and VPA-treated animals in presence of KA-induced seizures improved in the memory swim task, possibly due to the neuroprotection associated with these ADs (e.g. KA: 43s v. LTG+KA: 29.1s). While the ADs demonstrated some beneficial effects by attenuating seizure-induced memory impairment, poor antiepileptic activity and other deleterious side-effects were also observed at young ages suggesting that new drugs to aid epilepsy in children and adolescents are still required. (Supported by New York College of Osteopathic Medicine of NYIT and NJ Neuroscience Institute.)