Normal spatial and contextual learning for ketamine-treated rats in the pilocarpine epilepsy model

Abstract

Cognitive impairments frequently accompany epileptic disorders. Here, we examine two neuroprotective agents, the noncompetitive NMDA antagonist ketamine and the dopaminergic antagonist acepromazine, for their efficacy in attenuating cognitive impairments in the lithium–pilocarpine (LI–PILO) model of rat limbic epilepsy. Declarative-like cognitive behaviors were assessed in a Morris water maze task that consisted successively of spatial and nonspatial (cued platform) training. Whereas the ketamine-treated (Ket) LI–PILO rats performed equally in all respects to nonseized control rats for the spatial and nonspatial components of the water maze task, the acepromazine-treated (Ace) LI–PILO rats failed to demonstrate learning in either the hidden or cued platform variants of the task and did not demonstrate any place learning in the platform-removed probe trials. We further assessed nondeclarative (associative) cognitive behaviors with a standard contextual fear-conditioning protocol. LI–PILO rats treated with acepromazine failed to learn the Pavlovian relationship; Ket LI–PILO rats performed equivalently to nonseized controls. Cumulatively, these data suggest robust cognitive sparing for LI–PILO rats with pharmacological NMDA receptor antagonism following induction of status epilepticus (SE). This cognitive sparing occurs despite earlier findings that the mean amount of total brain damage with LI–PILO is equivalent for Ket and Ace rats.