title: Seizure susceptibility and epileptogenesis in a rat model of epilepsy and depression co-morbidity.
abstract: 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.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: S Alisha
authors.initials: SA
authors.lastname: Epps
authors.forename: Kroshona D
authors.initials: KD
authors.lastname: Tabb
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Lin
authors.forename: Alexa B
authors.initials: AB
authors.lastname: Kahn
authors.forename: Martin A
authors.initials: MA
authors.lastname: Javors
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Boss-Williams
authors.forename: Jay M
authors.initials: JM
authors.lastname: Weiss
authors.forename: David
authors.initials: D
authors.lastname: Weinshenker
mesh_terms: D000679:Amygdala / Q000502:physiology; D000818:Animals; D015897:Comorbidity; D003863:Depression / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006624:Hippocampus / Q000502:physiology; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology