Genetic background contributes to the co-morbidity of anxiety and depression with audiogenic seizure propensity and responses to fluoxetine treatment

Sarkisova, K. Yu.; Федотова, И. Б.; Сурина, Н. М.; Nikolaev, G. S.; Perepelkina, O. V.; Kostina, Zoya A.; Полетаева, И. И.

doi:10.1016/j.yebeh.2016.12.025

Cited by 20 publications

(19 citation statements)

References 49 publications

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“…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 ). In the light-dark test, GEPR-3s had reduced time spent in the light chamber of the apparatus; this phenotype extends beyond conflict-exploratory tests into unconditioned fear: when challenged with a looming visual stimulus, GEPR-3s displayed increased freezing in the post-stimulus period.…”

Section: Discussionsupporting

confidence: 90%

“…Serotonin is also a regulator of seizure susceptibility in GEPR-3s ( 69 , 75 ), and accordingly, treatment with fluoxetine, a selective serotonin reuptake inhibitor that is primarily used for the treatment of depression and generalized anxiety, results in a decrease in AGS severity ( 9 ). In KM rats, fluoxetine, reduced immobility in the forced swim task ( 68 ), although it had no effect on EPM behavior. The degree to which serotonin-based pharmacotherapy would normalize behavioral co-morbidities in the GEPR-3 remains to be explored.…”

Section: Discussionmentioning

confidence: 96%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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Epilepsy is associated with a variety of neuropsychiatric comorbidities, including both anxiety and depression. Despite high occurrences of depression and anxiety seen in human epilepsy populations, little is known about the etiology of these comorbidities. Experimental models of epilepsy provide a platform to disentangle the contribution of acute seizures, genetic predisposition, and underlying circuit pathologies to anxious and depressive phenotypes. Most studies to date have focused on comorbidities in acquired epilepsies; genetic models, however, allow for the assessment of affective phenotypes that occur prior to onset of recurrent seizures. Here, we tested male and female genetically epilepsy-prone rats (GEPR-3s) and Sprague-Dawley controls in a battery of tests sensitive to anxiety-like and depressive-like phenotypes. GEPR-3s showed increased anxiety-like behavior in the open field test, elevated plus maze, light-dark transition test, and looming threat test. Moreover, GEPR-3s showed impaired prepulse inhibition of the acoustic startle reflex, decreased sucrose preference index, and impaired novel object recognition memory. We also characterized defense behaviors in response to stimulation thresholds of deep and intermediate layers of the superior colliculus (DLSC), but found no difference between strains. In sum, GEPR-3s showed inherited anxiety, an effect that did not differ significantly between sexes. The anxiety phenotype in adult GEPR-3s suggests strong genetic influences that may underlie both the seizure disorder and the comorbidities seen in epilepsy.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…К настоящему времени подобных экспериментов с другими линиями крыс, предрасположенными к АЭ, не проводилось. С вопросом генетической основы АЭ и «коморбидных» этому признаку патологических признаков связаны недавно полученные данные по реакции крыс четырех генотипов (КМ, «4», «0» и Вистар) на хроническое введение ингибитора обратного захвата моноаминов флуоксетина (Sarkisova et al, 2017). Использование в этих экспериментах линий «0» и «4» наряду с КМ и Вистар позволило показать, что наличие у крыс АЭ (КМ и «4») и ее отсутствие («0» и Вистар) не связано с различиями в проявлении тревожности и склонности к развитию подобных депрессии состояний.…”

Section: аудиогенная эпилепсия (краткий обзор)unclassified

The Krushinsky – Molodkina genetic rat strain as a unique experimental model of seizure states

Полетаева¹,

Kostyna²,

Сурина³

et al. 2017

Vestn. VOGiS

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“…Depression and anxiety are the most prevalent comorbidities of different types of convulsive and non‐convulsive epilepsies in humans and animal models . Although there is evidence for a substantial genetic component for epilepsy and depression, it is likely that a combination of genetic and environmental factors leading to epigenetic modifications contribute to their complex pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Maternal care exerts disease‐modifying effects on genetic absence epilepsy and comorbid depression

Sarkisova

Gabova

2018

Genes Brain and Behavior

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WAG/Rij rats, a genetic animal model of absence epilepsy with comorbidity of depression, exhibit behavioral depression-like symptoms and spontaneous generalized spike-wave discharges (SWDs) in the EEG at the age of 6 to 8 months. The aim of the present study was to test the hypothesis that maternal care is an environmental factor which, along with genetic predisposition, may contribute to the expression of absence seizures and depression-like comorbidity later in life. To achieve this, a cross-fostering procedure was used. EEG and behavior in the forced swimming test were analyzed in WAG/Rij and Wistar offspring reared by their own mothers (non-cross-fostered), foster mothers of the same strain (in-fostered) or another strain (cross-fostered) at the age of 7 to 8 months. Maternal care and forced swimming test behavior were assessed in the dams. WAG/Rij mothers showed depression-like behavior and reduced maternal care irrespective of litter size and litter composition (own or foster pups) compared with Wistar dams. WAG/Rij offspring reared by Wistar dams with a high level of maternal care exhibited less and shorter SWDs and reduced depression-like comorbidity in adulthood compared with age-matched WAG/Rij offspring reared by their own or foster WAG/Rij mothers with a low level of maternal care. Moreover, rearing by Wistar mothers delayed the onset of absence epilepsy in WAG/Rij rats. Adoption by WAG/Rij dams did not change EEG and behavior in Wistar rats. Our study demonstrates that improvement of early care-giving environment can be used as a disease-modifying treatment to counteract epileptogenesis and behavioral comorbidities in genetic absence epilepsy.

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Genetic background contributes to the co-morbidity of anxiety and depression with audiogenic seizure propensity and responses to fluoxetine treatment

Cited by 20 publications

References 49 publications

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

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

The Krushinsky – Molodkina genetic rat strain as a unique experimental model of seizure states

Maternal care exerts disease‐modifying effects on genetic absence epilepsy and comorbid depression

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