Attention and executive functions in a rat model of chronic epilepsy

Epilepsia. 2014 May;55(5):644-653. doi: 10.1111/epi.12549. Epub 2014 Feb 22.

Abstract

Objective: Temporal lobe epilepsy is a relatively frequent, invalidating, and often refractory neurologic disorder. It is associated with cognitive impairments that affect memory and executive functions. In the rat lithium-pilocarpine temporal lobe epilepsy model, memory impairment and anxiety disorder are classically reported. Here we evaluated sustained visual attention in this model of epilepsy, a function not frequently explored.

Methods: Thirty-five Sprague-Dawley rats were subjected to lithium-pilocarpine status epilepticus. Twenty of them received a carisbamate treatment for 7 days, starting 1 h after status epilepticus onset. Twelve controls received lithium and saline. Five months later, attention was assessed in the five-choice serial reaction time task, a task that tests visual attention and inhibitory control (impulsivity/compulsivity). Neuronal counting was performed in brain regions of interest to the functions studied (hippocampus, prefrontal cortex, nucleus basalis magnocellularis, and pedunculopontine tegmental nucleus).

Results: Lithium-pilocarpine rats developed motor seizures. When they were able to learn the task, they exhibited attention impairment and a tendency toward impulsivity and compulsivity. These disturbances occurred in the absence of neuronal loss in structures classically related to attentional performance, although they seemed to better correlate with neuronal loss in hippocampus. Globally, rats that received carisbamate and developed motor seizures were as impaired as untreated rats, whereas those that did not develop overt motor seizures performed like controls, despite evidence for hippocampal damage.

Significance: This study shows that attention deficits reported by patients with temporal lobe epilepsy can be observed in the lithium-pilocarpine model. Carisbamate prevents the occurrence of motor seizures, attention impairment, impulsivity, and compulsivity in a subpopulation of neuroprotected rats.

Keywords: 5-CSRTT; Attention; Impulsivity/compulsivity; Lithium-pilocarpine; Temporal lobe epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Attention* / drug effects
  • Attention* / physiology
  • Brain / drug effects
  • Brain / physiopathology
  • Brain Mapping
  • Carbamates / pharmacology
  • Cell Count
  • Disease Models, Animal*
  • Epilepsy, Complex Partial / chemically induced
  • Epilepsy, Complex Partial / physiopathology
  • Epilepsy, Complex Partial / psychology*
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / physiopathology
  • Epilepsy, Temporal Lobe / psychology*
  • Executive Function* / drug effects
  • Executive Function* / physiology
  • Inhibition, Psychological
  • Lithium Carbonate
  • Neurons / drug effects
  • Neurons / physiology
  • Pattern Recognition, Visual / drug effects
  • Pattern Recognition, Visual / physiology
  • Pilocarpine
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Serial Learning / drug effects
  • Serial Learning / physiology
  • Status Epilepticus / chemically induced
  • Status Epilepticus / physiopathology
  • Status Epilepticus / psychology*

Substances

  • Anticonvulsants
  • Carbamates
  • S-2-O-carbamoyl-1-o-chlorophenyl-ethanol
  • Pilocarpine
  • Lithium Carbonate