Seizure Susceptibility and Epileptogenesis in a Rat Model of Epilepsy and Depression Co-Morbidity
| Autor: | Kroshona D Tabb, Katherine A. Boss-Williams, Jay M. Weiss, Alexa Kahn, Sharon J. Lin, S. Alisha Epps, Martin A. Javors, David Weinshenker |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Hippocampus Comorbidity Status epilepticus Hippocampal formation Epileptogenesis Amygdala Rats Mutant Strains Epilepsy Seizures medicine Animals Genetic Predisposition to Disease Pharmacology Depression Kindling medicine.disease Rats Disease Models Animal Psychiatry and Mental health medicine.anatomical_structure Pilocarpine Original Article medicine.symptom Psychology Neuroscience medicine.drug |
| Zdroj: | Neuropsychopharmacology. 37:2756-2763 |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/npp.2012.141 |
| Popis: | Although a strong co-morbidity exists clinically between epilepsy and depression, the cause of this co-morbidity remains unknown, and a valid animal model is crucial for the identification of underlying mechanisms and the development of a screening tool for novel therapies. Although some rodent models of epilepsy have been reported to display behaviors relevant to affective disorders, the seizure susceptibility of animals prone to depression-like behavior has not been characterized. Toward this end, we assessed several forms of seizure sensitivity and epileptogenesis in rats selectively bred for vulnerability (Swim Lo-Active; SwLo) or resilience (Swim High-Active; SwHi) to depression-like phenotypes. The SwLo rats exhibit decreased motor activity in a swim test and other depression-like phenotypes, whereas the SwHi rats display increased motor activity in a swim test. SwLo rats exhibited a decreased latency to limbic motor seizures following acute pilocarpine administration in the absence of differences in pilocarpine pharmacokinetics, and also had a decreased threshold to tonic seizures induced by electroshock. Approximately half of the SwLo rats, but none of the SwHi rats, had spontaneous limbic motor seizures 5 weeks following pilocarpine-induced status epilepticus. While the number of stimulations required to achieve full amygdala and hippocampal electrical kindling were similar in the two rat lines, SwLo rats had a lower final hippocampal kindling threshold and more wet dog shakes during both amygdala and hippocampal kindling. Combined, these results indicate that SwLo rats are a model of epilepsy and depression co-morbidity that can be used for investigating underlying neurobiological and genetic mechanisms and screening novel therapeutics. |
| Databáze: | OpenAIRE |
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