A comprehensive behavioral evaluation in the lithium-pilocarpine model in rats: effects of carisbamate administration during status epilepticus

Epilepsia. 2013 Jul;54(7):1203-13. doi: 10.1111/epi.12219. Epub 2013 May 11.

Abstract

Purpose: Administration of carisbamate during status epilepticus (SE) prevents the occurrence of motor seizures in the lithium-pilocarpine model and leads in a subpopulation of rats to spike-and-wave discharges characteristic of absence epilepsy. Widespread neuroprotection accompanied this change in seizure expression. To assess whether these carisbamate-induced changes affected comorbidity, we used a large battery of behavioral tests in rats that had developed temporal lobe or absence-like seizures.

Methods: Lithium-pilocarpine or saline was administered to 60 adult rats. Carisbamate (90 mg/kg) or diazepam and saline was given 1 h after SE onset, and repeated 8 h later and twice daily over 6 more days. Rats were video-monitored for 2 months. Subsequently, locomotor activity, anxiety, and various types of memory were assessed.

Key findings: In rats with motor seizures, treated or not with carisbamate, all features of behavior were impaired compared to controls. Rats exhibiting absence-like seizures after carisbamate treatment behaved as controls in all paradigms tested along with widespread neuroprotection.

Significance: Carisbamate treatment leading to absence-like instead of temporal lobe seizures impressively prevented behavioral comorbidities reported by patients with epilepsy as the most disabling.

Keywords: Carisbamate; Learning and memory; Lithium-pilocarpine; Neuroprotection; Temporal lobe epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage*
  • Antipsychotic Agents / toxicity
  • Behavior, Animal / drug effects*
  • Brain / pathology
  • Carbamates / administration & dosage*
  • Cell Count
  • Disease Models, Animal
  • Lithium / toxicity
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / pathology
  • Muscarinic Agonists / toxicity
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Phosphopyruvate Hydratase / metabolism
  • Pilocarpine / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Status Epilepticus / chemically induced
  • Status Epilepticus / drug therapy*
  • Status Epilepticus / pathology
  • Status Epilepticus / physiopathology*
  • Visual Perception / drug effects

Substances

  • Anticonvulsants
  • Antipsychotic Agents
  • Carbamates
  • Muscarinic Agonists
  • S-2-O-carbamoyl-1-o-chlorophenyl-ethanol
  • Pilocarpine
  • Lithium
  • Phosphopyruvate Hydratase