{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:39Z","timestamp":1787028579138,"version":"build-2736575974"},"reference-count":94,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Assignment of the Ministry of Education and Science of the Russian Federation to the Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences","award":["1021062411628-8-3.1.4"],"award-info":[{"award-number":["1021062411628-8-3.1.4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Depression is the most common psychiatric disorder and is frequently comorbid with epilepsy. Despite the high incidence of depression in epilepsy and the well-established sex differences in depression in clinical studies, sex differences in depression in epilepsy models remain unclear. This study aimed to investigate sex differences in depression comorbid with absence epilepsy and their neurochemical mechanisms in the WAG\/Rij rat model. WAG\/Rij rats, regardless of sex, exhibited symptoms of depression-like behaviour in the forced swimming test: increased immobility and decreased climbing, swimming, and diving. Both strain and sex differences were found in sucrose preference and splash tests, indicating anhedonia. However, anhedonia was more pronounced in WAG\/Rij females compared to males. Unlike the males, WAG\/Rij females showed signs of increased anxiety, suggesting an anxious depression phenotype. In WAG\/Rij rats compared to Wistar controls, a reduced content of dopamine and its metabolites in brain structures was revealed, indicating a reduced dopaminergic tone of the brain. In WAG\/Rij females compared to males, a more pronounced dopamine insufficiency and alterations in serotonin metabolism were found. The results indicate that sex differences in neurochemical alterations in brain structures may underlie sex differences in the manifestation of depressive pathology in the WAG\/Rij rat preclinical model.<\/jats:p>","DOI":"10.3390\/ijms27052154","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T09:31:32Z","timestamp":1772098292000},"page":"2154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The WAG\/Rij Rat Model of Depression Comorbid with Absence Epilepsy: Sex Differences and Neurochemical Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-7003","authenticated-orcid":false,"given":"Karine Yu.","family":"Sarkisova","sequence":"first","affiliation":[{"name":"Experimental Pathology of the Nervous System Group, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir S.","family":"Kudrin","sequence":"additional","affiliation":[{"name":"Neurochemical Pharmacology Group, Federal State Budgetary Institution \u201cScientific Research Institute of Pharmacology named after V.V. Zakusov\u201d, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, G.-Y., Fu, F.-J., Chou, Y.-X., Ye, M.-S., Ouyang, Y.-L., Yan, M.-D., Pan, L., Li, W.-P., and Xie, W. (2024). Frontiers and hotspots in comorbid epilepsy and depression: A bibliometric analysis from 2003 to 2023. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1413582"},{"key":"ref_2","first-page":"932","article-title":"Directionality of the association between epilepsy and depression: A nationwide register-based cohort study","volume":"100","author":"Dreier","year":"2023","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12955-022-01960-8","article-title":"The Chinese version of the quality of life in childhood epilepsy questionnaire-16-C (QOLCE-16-C): Translation, validity, and reliability","volume":"20","author":"Tang","year":"2022","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.yebeh.2012.01.007","article-title":"Depression and epilepsy: Epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence","volume":"24","author":"Kanner","year":"2012","journal-title":"Epilepsy Behav."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S0006-3223(03)00469-4","article-title":"Depression in epilepsy: Prevalence, clinical semiology, pathogenic mechanisms, and treatment","volume":"54","author":"Kanner","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_6","first-page":"e18761429380394","article-title":"Exploring the immune-related molecular mechanisms underlying the comorbidity of temporal lobe epilepsy and major depressive disorder through integrated data set analysis","volume":"17","author":"Yan","year":"2024","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/epi.13786","article-title":"Neurobehavioral comorbidities of epilepsy: Role of inflammation","volume":"58","author":"Mazarati","year":"2017","journal-title":"Epilepsia"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bowman, R., Frankfurt, M., and Luine, V. (2025). Sex differences in anxiety and depression: Insights from adult rodent models of chronic stress and neural plasticity. Front. Behav. Neurosci., 19.","DOI":"10.3389\/fnbeh.2025.1591973"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Guo, W., Li, Y.X., Zhang, Y., Lv, X.R., Wang, S.X., Zhang, S.Y., Wang, E.-S., Chen, X.-J., and Li, Y. (2023). Risk analysis of depression among adult patients with epilepsy of different sex: A retrospective single-center study from China. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1283983"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107801","DOI":"10.1016\/j.yebeh.2021.107801","article-title":"Sex differences in anxiety in patients with epilepsy: Status and risk factors analysis","volume":"116","author":"Zhong","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/09540261.2017.1302412","article-title":"Psychiatric comorbidities in epilepsy","volume":"29","author":"Josephson","year":"2017","journal-title":"Int. Rev. Psychiatry"},{"key":"ref_12","first-page":"S81","article-title":"Factors not considered in the study of drug-resistant epilepsy: Psychiatric comorbidities, age, and gender","volume":"7","author":"Escalante","year":"2022","journal-title":"Epilepsia Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.yfrne.2014.05.004","article-title":"Sex differences in anxiety and depression clinical perspectives","volume":"35","author":"Altemus","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1124\/pr.119.017392","article-title":"Sex Differences in the epilepsies and associated comorbidities: Implications for use and development of pharmacotherapies","volume":"72","author":"Christian","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105733","DOI":"10.1016\/j.psyneuen.2022.105733","article-title":"Commonly-used rodent tests of anxiety-like behavior lack predictive validity for human sex differences","volume":"141","author":"Borchers","year":"2022","journal-title":"Psychoneuroendocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.expneurol.2007.09.026","article-title":"Elevated anxiety and depressive-like behavior in a rat model of genetic generalized epilepsy suggesting common causation","volume":"209","author":"Jones","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0166-4328(03)00090-1","article-title":"Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in WAG\/Rij rats with genetic absence epilepsy","volume":"144","author":"Sarkisova","year":"2003","journal-title":"Behav. Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yebeh.2016.12.025","article-title":"Genetic background contributes to the comorbidity of anxiety and depression with audiogenic seizure propensity and responses to fluoxetine treatment","volume":"68","author":"Sarkisova","year":"2017","journal-title":"Epilepsy Behav."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1093\/brain\/awn117","article-title":"Depression after status epilepticus: Behavioural and biochemical deficits and effects of fluoxetine","volume":"131","author":"Mazarati","year":"2008","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.bcp.2012.08.016","article-title":"Rhythm and blues: Animal models of epilepsy and depression comorbidity","volume":"85","author":"Epps","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.yebeh.2017.10.025","article-title":"Seizure-induced activation of the HPA axis increases seizure frequency and comorbid depression-like behaviors","volume":"78","author":"Hooper","year":"2018","journal-title":"Epilepsy Behav."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"ENEURO.0158-0118.2018","DOI":"10.1523\/ENEURO.0158-18.2018","article-title":"Targeting the mouse ventral hippocampus in the intrahippocampal kainic acid model of temporal lobe epilepsy","volume":"5","author":"Zeidler","year":"2018","journal-title":"eNeuro"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Aguilar, B.L., Malkova, L., N\u2019Gouemo, P., and Forcelli, P.A. (2018). Genetically epilepsy-prone rats display anxiety-like behaviors and neuropsychiatric comorbidities of epilepsy. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00476"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1023\/A:1026179013847","article-title":"Genetic animal models for absence epilepsy: A review of the WAG\/Rij strain of rats","volume":"33","author":"Coenen","year":"2003","journal-title":"Behav. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.neubiorev.2016.09.017","article-title":"Upholding WAG\/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development","volume":"71","author":"Russo","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1528-1167.2009.02260.x","article-title":"Spike-wave discharges are necessary for the expression of behavioral depression-like symptoms","volume":"51","author":"Sarkisova","year":"2010","journal-title":"Epilepsia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.pnpbp.2010.11.010","article-title":"The WAG\/Rij strain: A genetic animal model of absence epilepsy with comorbidity of depression","volume":"35","author":"Sarkisova","year":"2011","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1111\/j.1528-1167.2011.03112.x","article-title":"Effects of early long-term treatment with antiepileptic drugs on development of seizures and depressive-like behavior in a rat genetic absence epilepsy model","volume":"52","author":"Russo","year":"2011","journal-title":"Epilepsia"},{"key":"ref_29","first-page":"303","article-title":"Neurochemical mechanisms of depression-like behavior in WAG\/Rij rats","volume":"63","author":"Sarkisova","year":"2013","journal-title":"Zhurnal Vyss. Nervn. Deiatelnosti Im. IP Pavlov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1177\/02698811231200881","article-title":"Dopamine in major depressive disorder: A systematic review and meta-analysis of in vivo imaging studies","volume":"37","author":"Mizuno","year":"2023","journal-title":"J. Psychopharmacol."},{"key":"ref_31","first-page":"4","article-title":"Relationship of neurotransmitters to the symptoms of major depressive disorder","volume":"69","author":"Nutt","year":"2008","journal-title":"J. Clin. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhao, F., Cheng, Z., Piao, J., Cui, R., and Li, B. (2022). Dopamine receptors: Is it possible to become a therapeutic target for depression?. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.947785"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1111\/epi.16342","article-title":"Early reduced dopaminergic tone mediated by D3 receptor and dopamine transporter in absence epileptogenesis","volume":"60","author":"Cavarec","year":"2019","journal-title":"Epilepsia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e12477","DOI":"10.1111\/gbb.12477","article-title":"Maternal care exerts disease-modifying effects on genetic absence epilepsy and comorbid depression","volume":"17","author":"Sarkisova","year":"2018","journal-title":"Genes Brain Behav."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sarkisova, K.Y., Fedosova, E.A., Shatskova, A.B., Rudenok, M.M., Stanishevskaya, V.A., and Slominsky, P.A. (2023). Maternal methyl-enriched diet increases DNMT1, HCN1, and TH gene expression and suppresses absence seizures and comorbid depression in offspring of WAG\/Rij rats. Diagnostics, 13.","DOI":"10.3390\/diagnostics13030398"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1111\/j.1460-9568.2006.04865.x","article-title":"Environmental manipulations early in development alter seizure activity, Ih, and HCN1 protein expression later in life","volume":"23","author":"Schridde","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.ibneur.2022.10.012","article-title":"The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities","volume":"13","author":"Sarkisova","year":"2022","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_38","first-page":"624","article-title":"Behavioral characteristics of female WAG\/Rij rats","volume":"61","author":"Sarkisova","year":"2011","journal-title":"Zhurnal Vyss. Nervn. Deiatelnosti Im. IP Pavlov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1097\/00008877-200312000-00005","article-title":"The effects of 7-OH-DPAT, quinpirol and raclopride on licking for sucrose solutions in the non-deprived rat","volume":"14","author":"Genn","year":"2003","journal-title":"Behav. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Markov, D.D. (2022). Sucrose preference test as a measure of anhedonic behavior in a chronic unpredictable mild stress model of depression: Outstanding issues. Brain Sci., 12.","DOI":"10.3390\/brainsci12101287"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neubiorev.2016.03.004","article-title":"Assessing anhedonia in depression: Potentials and pitfalls","volume":"65","author":"Rizvi","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1037\/abn0000244","article-title":"Anticipatory and consummatory pleasure and displeasure in major depressive disorder: An experience sampling study","volume":"126","author":"Wu","year":"2017","journal-title":"J. Abnorm. Psychol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1159\/000087097","article-title":"Chronic mild stress (CMS) revisited: Consistency and behavioural-neurobiological concordance in the effects of CMS","volume":"52","author":"Willner","year":"2005","journal-title":"Neuropsychobiology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Pitzer, C., Kurpiers, B., and Eltokhi, A. (2022). Sex differences in depression-like behaviors in adult mice depend on endophenotype and strain. Front. Behav. Neurosci., 16.","DOI":"10.3389\/fnbeh.2022.838122"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3390\/sexes3010012","article-title":"Sex differences in anxiety and depression: What can (and cannot) preclinical studies tell us?","volume":"3","author":"Mir","year":"2022","journal-title":"Sexes"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.neuropharm.2015.03.016","article-title":"Forced swim test: What about females?","volume":"99","author":"Kokras","year":"2015","journal-title":"Neuropharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0014-2999(00)00491-X","article-title":"Sex differences in forced-swim and open-field test behaviours after chronic administration of melatonin","volume":"402","author":"Brotto","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbr.2005.07.024","article-title":"Behavioral characteristics of WAG\/Rij rats susceptible and non-susceptible to audiogenic seizures","volume":"166","author":"Sarkisova","year":"2006","journal-title":"Behav. Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/dev.22037","article-title":"Sex and age differences in locomotor and anxiety-like behaviors in rats: From adolescence to adulthood","volume":"63","author":"Bishnoi","year":"2021","journal-title":"Dev. Psychobiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0091-3057(99)00168-9","article-title":"Gender differences in dopaminergic function in striatum and nucleus accumbens","volume":"64","author":"Becker","year":"1999","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_51","first-page":"27","article-title":"Modulation of brain dopamine transmission by sex steroids","volume":"5","year":"1994","journal-title":"Rev. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"126","DOI":"10.7150\/ijbs.4.126","article-title":"Sex hormones\u2019 regulation of rodent physical activity: A review","volume":"4","author":"Lightfoot","year":"2008","journal-title":"Int. J. Biol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1196\/annals.1432.010","article-title":"Sex difference in dopamine and vesicular monoamine-transporter functions","volume":"1139","author":"Dluzen","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13293-020-00285-9","article-title":"Sex difference in dopamine D1-D2 receptor complex expression and signaling affects depression- and anxiety-like behaviors","volume":"11","author":"Hasbi","year":"2020","journal-title":"Biol. Sex Differ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1192\/bjp.177.6.486","article-title":"Gender differences in depression. Critical review","volume":"177","author":"Piccinelli","year":"2000","journal-title":"Br. J. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2042-6410-3-14","article-title":"Sex differences in the neural mechanisms mediating addiction: A new synthesis and hypothesis","volume":"3","author":"Becker","year":"2012","journal-title":"Biol. Sex Differ."},{"key":"ref_57","first-page":"668","article-title":"Age-related changes in behavior, in monoamines and their metabolites content, and in density of Dl and D2 dopamine receptors in the brain structures of WAG\/Rij rats with depression-like pathology","volume":"64","author":"Sarkisova","year":"2014","journal-title":"Zhurnal Vyss. Nervn. Deiatelnosti Im. IP Pavlov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/j.1471-4159.1991.tb03802.x","article-title":"Interstitial 3-methoxytyramine reflects striatal dopamine release: An in vivo microdialysis study","volume":"57","author":"Brown","year":"1991","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1038\/s41380-019-0484-3","article-title":"Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion","volume":"25","author":"Coimbra","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.neuron.2019.03.003","article-title":"A motivational and neuropeptidergic hub: Anatomical and functional diversity within the nucleus accumbens shell","volume":"102","author":"Castro","year":"2019","journal-title":"Neuron"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1038\/ncomms8062","article-title":"Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression","volume":"6","author":"Bagot","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.biopsych.2005.09.018","article-title":"The mesolimbic dopamine reward circuit in depression","volume":"59","author":"Nestler","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1134\/S001249662205012X","article-title":"Maternal methyl-enriched diet increases dopaminergic tone in the mesolimbic brain system in adult offspring of WAG\/Rij rats","volume":"506","author":"Sarkisova","year":"2022","journal-title":"Dokl. Biol. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1152\/ajpregu.00282.2003","article-title":"Oral sucrose stimulation increases accumbens dopamine in the rat","volume":"286","author":"Hajnal","year":"2004","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbr.2013.10.035","article-title":"Induction of depressive-like behavior by intranigral 6-OHDA is directly correlated with deficits in striatal dopamine and hippocampal serotonin","volume":"259","author":"Santiago","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"MacDonald, H.J., Kleppe, R., Szigetvari, P.D., and Haavik, J. (2024). The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1492126"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1037\/0033-295X.114.4.1047","article-title":"Stimulus-dependent dopamine release in attention-deficit\/hyperactivity disorder","volume":"114","year":"2007","journal-title":"Psychol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/00008877-200111000-00013","article-title":"Dopamine characteristics in rat genotypes with distinct susceptibility to epileptic activity: Apomorphine-induced stereotyped gnawing and novelty\/amphetamine-induced locomotor stimulation","volume":"12","author":"Cools","year":"2001","journal-title":"Behav. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1097\/YCO.0000000000000376","article-title":"Parients with anxious depression: Overview of prevalence, pathophysiology and impact on course and treatment outcome","volume":"31","author":"Gaspersz","year":"2018","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1007\/s00702-019-02069-x","article-title":"Anxious depression as a clinically relevant subtype of pediatric major depressive disorder","volume":"126","author":"Baumgartner","year":"2019","journal-title":"J. Neural. Transm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"107985","DOI":"10.1016\/j.neuropharm.2020.107985","article-title":"Median raphe serotonin neurons promote anxiety-like behavior via inputs to the dorsal hippocampus","volume":"168","author":"Abela","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0920-1211(87)90005-2","article-title":"The WAG\/Rij rat model for absence epilepsy: Age and sex factors","volume":"1","author":"Coonen","year":"1987","journal-title":"Epilepsy Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.nbd.2014.08.014","article-title":"Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?","volume":"72","author":"Onat","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0304-3940(82)90136-7","article-title":"Spontaneous paroxysmal electroclinical patterns in rat: A model of generalized non-convulsive epilepsy","volume":"3","author":"Vergnes","year":"1982","journal-title":"Neurosci. Letters"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"106693","DOI":"10.1016\/j.eplepsyres.2021.106693","article-title":"Absence epilepsy in male and female WAG\/Rij rats: A longitudinal EEG analysis of seizure expression","volume":"176","author":"Palmer","year":"2021","journal-title":"Epilepsy Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.expneurol.2017.06.022","article-title":"Sociability impairments in Genetic Absence Epilepsy Rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944","volume":"296","author":"Henbid","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1601-183X.2006.00249.x","article-title":"Estrous cycle effects on behavior of C57BL\/6J and BALB\/cByJ female mice: Implications for phenotyping strategies","volume":"6","author":"Meziane","year":"2007","journal-title":"Genes Brain Behav."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"112670","DOI":"10.1016\/j.physbeh.2019.112670","article-title":"Sex differences in anxiety-like behaviors in rats","volume":"211","author":"Scholl","year":"2019","journal-title":"Physiol. Behav."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lovick, T.A., and Zangrossi, H. (2021). Effect pf estrous cycle on behavior in females in rodent tests of anxiety. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.711065"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"104962","DOI":"10.1016\/j.neubiorev.2022.104962","article-title":"Female rodents are not more variable than male rodents: A meta-analysis of preclinical studies of fear and anxiety","volume":"143","author":"Kaluve","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2014.01.001","article-title":"Female mice liberated for inclusion in neuroscience and biomedical research","volume":"40","author":"Prendergast","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Zeng, P.-Y., Tsai, Y.-H., Lee, C.-L., Ma, Y.-K., and Kuo, T.-H. (2023). Minimal influence of estrous cycle on studies of female mouse behaviors. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1146109"},{"key":"ref_83","first-page":"325","article-title":"Repeated collection of vaginal smear causes stress in mice","volume":"59","author":"Varol","year":"2022","journal-title":"Arch. Neuropsych."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"104997","DOI":"10.1016\/j.beproc.2024.104997","article-title":"Three methods of behavioural testing to measure anxiety\u2014A review","volume":"215","author":"Chen","year":"2024","journal-title":"Behav. Processes"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4939-8994-2_9","article-title":"The open field test for measuring locomotor activity and anxiety-like behavior","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/10253890.2018.1438405","article-title":"Exploratory rearing: A context-and stress-sensitive behavior recorded in the open-field test","volume":"21","author":"Sturman","year":"2018","journal-title":"Stress"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0031-9384(94)00286-E","article-title":"Sucrose consumption as a hedonic measure following chronic unpredictable mild stress","volume":"57","author":"Mathews","year":"1995","journal-title":"Physiol. Behav."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/00008877-200205000-00001","article-title":"The validity of animal models of predisposition to depression","volume":"13","author":"Willner","year":"2002","journal-title":"Behav. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1038\/s41596-018-0011-z","article-title":"Sucrose preference test for measurement of stress-induced anhedonia in mice","volume":"13","author":"Liu","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/01.nmd.0000221425.04436.46","article-title":"Diagnosing major depressive disorder IV: Relationship between number of a symptoms and the diagnosis of disorder","volume":"194","author":"Zimmerman","year":"2006","journal-title":"J. Nerv. Ment. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Isingrini, E., Camus, V., Guisquet, A.M., Pingaud, M., Devers, S., and Belzung, C. (2010). Association between repeated unpredictable chronic mild stress (UCMS) procedures with a high fat diet: A model of fluoxetine resistance in mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010404"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/0471142301.ns0810as14","article-title":"Rodent models of depression: Forced swimming and tail suspension behavioral despair tests in rats and mice","volume":"14","author":"Porsolt","year":"2001","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nprot.2012.044","article-title":"Using the rat forced swim test to assess antidepressant-like activity in rodents","volume":"7","author":"Slattery","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Sarkisova, K.Y., Gabova, A.V., Fedosova, E.A., Shatskova, A.B., Narkevich, V.B., and Kudrin, V.S. (2023). Antidepressant and anxiolytic effects of L-Methionine in the WAG\/Rij rat model of depression comorbid with absence epilepsy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512425"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:25:49Z","timestamp":1772447149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":94,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052154"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052154","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]}}}