COMPARISON OF VALPROATE AND PHENOBARBITAL TREATMENT AFTER STATUS EPILEPTICUS IN RATS

Objective: To investigate the long-term effects of two widely used ant iepileptic medications, valproate and phenobarbital, on learning and b ehavior in the kainic acid (KA) model of epilepsy. Background: Prior c linical and animal studies have demonstrated that phenobarbital admini stered during development may result in subsequent cognitive impairmen t. It is unclear whether these adverse effects of phenobarbital extend to other antiepileptic drugs. Methods: A convulsant dose of KA.was ad ministered to rats on postnatal day (P) 35. From P36-75 rats received daily injections of phenobarbital (PH), valproate (VPA), or saline and spontaneous seizure frequency was monitored with video recordings. Af ter tapering of the drugs, the rats were tested in the water maze (a m easure of visuospatial memory) and handling test (a measure of emotion ality). Brains were then analyzed for histologic lesions. Results: KA caused status epilepticus in all the rats. In the PH- and saline-treat ed groups, there was impaired learning in the water maze, increased em otionality, recurrent seizures, and histologic lesions in the hippocam pal areas CA3, CA1, and dentate hilus. However, VPA-treated rats had n o spontaneous seizures, abnormalities in handling, or deficits in visu ospatial learning, and had fewer histologic lesions than animals recei ving KA alone. Conclusions: The long-term consequences of AED treatmen t during development are related to the drug used. VPA treatment after KA-induced status epilepticus prevents many of the neurologic sequela e typically seen after KA.