title: Effects of antiepileptic drugs on attention as assessed by a five-choice serial reaction time task in rats.
abstract: Patients with epilepsy can have impaired cognitive abilities. Antiepileptic drugs (AEDs) may contribute to the cognitive deficits observed in patients with epilepsy, and have been shown to induce cognitive impairments in healthy individuals. However, there are few systematic data on the effects of AEDs on specific cognitive domains. We have previously evaluated a number of AEDs with respect to their effects on working memory. The purpose of the present study was to evaluate the effects of AEDs on attention as measured by five-choice serial reaction time behavior in nonepileptic rats. The GABA-related AEDs triazolam, phenobarbital, and chlordiazepoxide significantly disrupted performance by increasing errors of omission, whereas tiagabine, valproate, and gabapentin did not. The sodium channel blocker carbamazepine increased errors of omission at relatively high doses, whereas the sodium channel blockers phenytoin, topiramate, and lamotrigine were without significant effect. Levetiracetam had no effect on attention. The disruptions produced by triazolam, phenobarbital, chlordiazepoxide, and carbamazepine were similar in magnitude to the effects of the muscarinic cholinergic receptor antagonist scopolamine. The present results indicate that AEDs can disrupt attention, but there are differences among AEDs in the magnitude of the disruption in nonepileptic rats, with drugs that enhance GABA receptor function producing the most consistent disruption of attention.
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. H.Shannon@Lilly.Com
authors.forename: Harlan E
authors.initials: HE
authors.lastname: Shannon
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Love
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018757:GABA Modulators / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D018757:GABA Modulators; D018727:Muscarinic Antagonists; D001569:Benzodiazepines; D012601:Scopolamine