Wistar audiogenic rats display abnormal behavioral traits associated with artificial selection for seizure susceptibility

Abstract

Accumulating evidence from different animal models has contributed to the understanding of the bidirectional comorbidity associations between the epileptic condition and behavioral abnormalities. A strain of animals inbred to enhance seizure predisposition to high-intensity sound stimulation, the Wistar audiogenic rat (WAR), underwent several behavioral tests: forced swim test (FST), open-field test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), social preference (SP), marble burying test (MBT), inhibitory avoidance (IAT), and two-way active avoidance (TWAA). The choice of tests aimed to investigate the correlation between underlying circuits believed to be participating in both WAR's innate susceptibility to sound-triggered seizures and the neurobiological substrates associated with test performance. Comparing WAR with its Wistar counterpart (i.e., resistant to audiogenic seizures) showed that WARs present behavioral despair traits (e.g., increased FST immobility) but no evidence of anhedonic behavior (e.g., increased sucrose consumption in SPT) or social impairment (e.g., no difference regarding juvenile exploration in SP). In addition, tests suggested that WARs are unable to properly evaluate degrees of aversiveness (e.g., performance on OFT, EPM, MBT, IAT, and TWAA). The particularities of the WAR model opens new venues to further untangle the neurobiology underlying the co-morbidity of behavioral disorders and epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Genetically Epilepsy-Prone Rats Display Anxiety-Like Behaviors and Neuropsychiatric Comorbidities of Epilepsy

“…Across standard tests of conflict-exploratory activity, GEPR-3s consistently displayed reduced exploration of aversive maze components. In the open field test, this was manifest as a reduced exploration of the center of the arena, in contrast with the increased exploration reported in WARs ( 67 ). In the EPM test, anxiety-like behavior was evident in fewer exploratory headpokes into the open arms of the maze, which is consistent with reports in KM rats ( 68 ).…”

“…AGS models such as the GEPR, the Wistar audiogenic rat (WAR), and Kurshinsky-Molodkina (KM) rat display increased susceptibility to acoustically-evoked generalized seizures, which are common in models of inherited epilepsy across species ( 64 – 66 ). Of these strains, the WAR and KM strains have been evaluated for comorbidities ( 67 , 68 ). While there has been some suggestion that the GEPR-3 strain may also display affective comorbidities ( 69 , 70 ), our data clearly demonstrate that comorbidity in GEPR-3s is an anxiety-like phenotype.…”

Exercise attenuates alveolar bone loss and anxiety‐like behaviour in rats with periodontitis

“…In the last week of the experiment (day 74), animals were submitted to the Marble Burying test for assessment of anxiety‐like‐behaviour, using the methodology described in previous studies (Castro et al., ; Lazic, ; Nicolas, Kolb, & Prinssen, ). This test was performed because of the anxious tendency rodents have to bury new objects, wherein the administration of anxiolytics reduces or inhibits this behaviour (Castro et al., ; Nicolas et al., ). To perform this test, a polypropylene box with the same dimensions as that used for their housing was used, containing five centimetres of wood shavings.…”

Estudo do metabolismo energético mitocondrial e sua relação com as crises epiléticas em Wistar audiogenic rats (WAR)

“…Observamos um aumento no conteúdo de proteínas da via glicolítica, da via de transaminação de aminoácidos e mTOR (síntese proteica). , 1994DORETTO et al, 2002DORETTO et al, , 2009SCARLATELLI-LIMA et al, 2003;ROMCY-PEREIRA;GARCIA-CAIRASCO, 2003;MAGALHÃES et al, 2004;GALVIS-ALONSO et al, 2004;ROSSETTI et al, 2006;PEREIRA et al, 2008;GITAÍ et al, 2011GITAÍ et al, , 2009GUEDES et al, 2009;CUNHA et al, 2015;TOTOLA et al, 2017;CASTRO et al, 2017). Apesar do maior consumo de oxigênio dos animais WAR em relação ao Wistar na região hipocampo, não observamos diferenças nas razões respiratórias entre os grupos (tabela 9).…”