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Distinct phenotypes, shared etiology: Dissociation of absence epilepsy, audiogenic seizures, and anhedonia in a genetic rat model

Evgenia Sitnikova1* ,  Maria Pupikina1
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1 Institute of the Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia
Advanced Neurology, 025010133 https://doi.org/10.36922/AN025010133
Received: 31 December 2025 | Revised: 10 February 2026 | Accepted: 28 February 2026 | Published online: 15 April 2026
(This article belongs to the Special Issue Advanced Neurology 3rd Anniversary Special Issue)
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Epilepsy is a heterogeneous neurological disorder, characterized by distinct seizure phenotypes. We examined the phenotypic expression of seizures in genetically predisposed rats, focusing on the relationship between absence epilepsy (AE), audiogenic seizures (AGS), and anhedonia. Thirty rats were assessed longitudinally for AE at 6 and 10 months and for AGS susceptibility. Anhedonia was measured using 2% sucrose preference test. Statistical analysis revealed a striking mutual exclusivity between seizure types: only 1 male among 11 AE-positive rats developed AGS, whereas 10 of 19 AE-negative rats (all females) developed AGS. Seizure manifestations in these rats exhibited a binary pattern, with a shared genetic predisposition affecting either corticothalamic or brainstem neural circuits, resulting in either AE or AGS, respectively. No association was found between either seizure phenotypes and anhedonia, as sucrose preference remained uniformly high across all groups. Logistic regression identified male sex as a negative predictor of AGS risk and confirmed the suppressive effect of AE on AGS susceptibility, although the models were limited by small sample size and strong collinearity between sex and sucrose preference. These results demonstrate circuit-specific phenotypic divergence in genetic epilepsy, with important implications for understanding seizure network development and comorbidity profiles.

Graphical abstract
Keywords
WAG/Rij rats
Sex dimorphism
Phenotypic exclusivity
Spike-and-wave discharges
Funding
The article was prepared in full within the state assignment of the Ministry of Education and Science of the Russian Federation to the Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, for 2024–2026.
Conflict of interest
The authors declare they have no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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