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

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.

• Authors: Jean-Baptiste Faure, Gladys Akimana, José E M Carneiro, Brigitte Cosquer, Arielle Ferrandon, Karin Geiger, Estelle Koning, Lorène Penazzi, Jean-Christophe Cassel, Astrid Nehlig
• Journal: Epilepsia (Epilepsia) Vol. 54 Issue 7 Pg. 1203-13 (Jul 2013) ISSN: 1528-1167 [Electronic] United States
• PMID: 23663139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Chemical References

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

Topics

• 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, pathology)
• Muscarinic Agonists (toxicity)
• Neurons (drug effects, metabolism, pathology)
• Phosphopyruvate Hydratase (metabolism)
• Pilocarpine (toxicity)
• Rats
• Rats, Sprague-Dawley
• Status Epilepticus (chemically induced, drug therapy, pathology, physiopathology)
• Visual Perception (drug effects)