Effects of antiepileptic drugs on working memory as assessed by spatial alternation performance in rats

Patients with epilepsy can have impaired cognitive abilities. Many factors contribute to this impairment, including the adverse effects of antiepileptic drugs (AEDs). However, there are few systematic data on the effects of AEDs on specific cognitive domains, such as working memory. The purpose of the present study was to evaluate the effects of AEDs on working memory as measured by delayed spatial alternation behavior in nonepileptic rats. The GABA-related AEDs triazolam and phenobarbital significantly disrupted performance, whereas tiagabine, valproate, and gabapentin did not. The sodium channel blockers carbamazepine and topiramate produced modest but significant disruption of performance, whereas the effects of lamotrigine were not significant and phenytoin produced a modest but significant improvement in performance but at doses that abolished responding in some animals. Levetiracetam had no effect on working memory. In contrast, ethosuximide significantly disrupted working memory. The disruptions produced by triazolam and phenobarbital were similar in magnitude to the effects of the muscarinic antagonist scopolamine. The present results indicate that AEDs can disrupt working memory, but there are differences among AEDs in the magnitude of the disruption that do not appear to be correlated with mechanism of action.