{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:03:49Z","timestamp":1790701429480,"version":"4.1.0"},"reference-count":96,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["25-44-10019"],"award-info":[{"award-number":["25-44-10019"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Background: Acute stress exposure can lead to delayed behavioral changes, which are widely regarded as core endophenotypes of post-traumatic stress disorder (PTSD). Identifying pre-existing behavioral traits that predict later maladaptive responses is crucial. We investigated whether early fear-related passive coping behavior during an active avoidance task predicts subsequent freezing reactions in a safe, stimulus-free environment. This context-inappropriate fear pattern may model individual vulnerability to PTSD-like symptoms. We used Wistar Albino rats from Rijswijk (WAG\/Rij rats), which are genetically predisposed to develop absence epilepsy. This condition is non-convulsive and characterized by sudden, brief periods of behavioral arrest known as absences. Absence-like seizures in WAG\/Rij rats are accompanied by spike-and-wave discharge (SWDs) on electroencephalogram (EEG) and behavioral arrest. We also examined the relationship between the severity of absence epilepsy and passive behavioral patterns in WAG\/Rij rats at symptomatic ages (10\u201312 months), as well as sex-related differences. Methods: We used an automated fear-conditioning paradigm to identify individual differences in baseline stress vulnerability that predict delayed, context-independent freezing behavior. Rats were tested in an active avoidance paradigm to assess fear-induced passive behavior under threat at the age of 9 months, and the percentage of passive behavioral responses was scored. Rats were then tested in a safe environment using the StartFear system, and the percentage of freezing was measured monthly at the ages of 10, 11, and 12 months. Finally, the rats underwent EEG examination, and SWDs were scored during 12-hour dark-phase recordings. Results: In the safe environment, 10- to 12-month-old WAG\/Rij rats exhibited low levels of freezing (9.5%\u201313.9% of the total time). No significant sex differences were observed in freezing behavior within the safe environment. However, in the unsafe, fear-inducing active avoidance task, males displayed significantly higher levels of passive behavior than females. Female rats showed strong correlations between passive responses in the fear-inducing situation and freezing in the safe environment, whereas males did not. Results from EEG examinations indicated that males exhibited a higher number of SWDs than females. Neither the percentage of freezing in the safe environment nor the percentage of passive responses in the active avoidance task correlated with the severity of absence epilepsy, as assessed by the number and duration of SWDs. WAG\/Rij rats tested after avoidance training exhibited low freezing in the StartFear paradigm and a sex-dependent increase in passive responses following conditioning; these findings are consistent with altered tonic inhibitory regulation but require na\u00efve controls and EEG-behavior coupling to establish causality. Conclusions: Four primary conclusions emerge from this study: (1) symptomatic WAG\/Rij rats exhibit low levels of freezing in a safe environment; (2) sex differences exist in unsafe contexts, but not safe ones; (3) there is a sex-dependent association between early passive behavior and later freezing; (4) there is no relationship between the severity of absence epilepsy and passive behavioral patterns. Therefore, thalamocortical disturbances associated with SWDs do not correlate with fear-related freezing or passive coping behaviors, suggesting a distinction between seizure-related immobility and non-seizure passive behaviors. There is also a sex-specific link between early passive coping and later context-inappropriate freezing, warranting further study in models of anxiety and PTSD.<\/jats:p>","DOI":"10.31083\/jin52427","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:16:31Z","timestamp":1790698591000},"source":"Crossref","is-referenced-by-count":0,"title":["Passive Behavioral Patterns in Symptomatic WAG\/Rij Rats: Dissociation From Absence Epilepsy and Sex-Dependent Link Between Early Fear Coping and Post-Stress Freezing"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2819-9096","authenticated-orcid":true,"given":"Evgenia","family":"Sitnikova","sequence":"first","affiliation":[{"name":"Institute of the Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9566-3402","authenticated-orcid":true,"given":"Maria","family":"Pupikina","sequence":"additional","affiliation":[{"name":"Institute of the Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7214-2845","authenticated-orcid":true,"given":"Aliya","family":"Vinarskaya","sequence":"additional","affiliation":[{"name":"Institute of the Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3967-3950","authenticated-orcid":true,"given":"Anton","family":"Kiselev","sequence":"additional","affiliation":[{"name":"Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref1","unstructured":"Torrico TJ, Mann SK, Marwaha R. Posttraumatic Stress Disorder. StatPearls Publishing: Treasure Island (FL), USA. 2026."},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Vieweg WV, Julius DA, Fernandez A, Beatty-Brooks M, Hettema JM, Pandurangi AK. Posttraumatic stress disorder: clinical features, pathophysiology, and treatment. The American Journal of Medicine. 2006; 119: 383\u2013390.","DOI":"10.1016\/j.amjmed.2005.09.027"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Bisson JI. Post-traumatic stress disorder. BMJ. 2007; 334: 789\u2013793.","DOI":"10.1136\/bmj.39162.538553.80"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Tortella-Feliu M, Fullana MA, P\u00e9rez-Vigil A, Torres X, Chamorro J, Littarelli SA, et al. Risk factors for posttraumatic stress disorder: An umbrella review of systematic reviews and meta-analyses. Neuroscience and Biobehavioral Reviews. 2019; 107: 154\u2013165.","DOI":"10.1016\/j.neubiorev.2019.09.013"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychological Medicine. 2017; 47: 2260\u20132274.","DOI":"10.1017\/S0033291717000708"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Benjet C, Bromet E, Karam EG, Kessler RC, McLaughlin KA, Ruscio AM, et al. The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychological Medicine. 2016; 46: 327\u2013343.","DOI":"10.1017\/S0033291715001981"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Alexander KS, Nalloor R, Bunting KM, Vazdarjanova A. Investigating Individual Pre-trauma Susceptibility to a PTSD-Like Phenotype in Animals. Frontiers in Systems Neuroscience. 2020; 13: 85.","DOI":"10.3389\/fnsys.2019.00085"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Dopfel D, Perez PD, Verbitsky A, Bravo-Rivera H, Ma Y, Quirk GJ, et al. Individual variability in behavior and functional networks predicts vulnerability using an animal model of PTSD. Nature Communications. 2019; 10: 2372.","DOI":"10.1038\/s41467-019-09926-z"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Panayiotopoulos CP. Typical absence seizures and related epileptic syndromes: assessment of current state and directions for future research. Epilepsia. 2008; 49: 2131\u20132139.","DOI":"10.1111\/j.1528-1167.2008.01777.x"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58: 522\u2013530.","DOI":"10.1111\/epi.13670"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Hirsch E, French J, Scheffer IE, Bogacz A, Alsaadi T, Sperling MR, et al. ILAE definition of the Idiopathic Generalized Epilepsy Syndromes: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63: 1475\u20131499.","DOI":"10.1111\/epi.17236"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Sadleir LG, Scheffer IE, Smith S, Carstensen B, Farrell K, Connolly MB. EEG features of absence seizures in idiopathic generalized epilepsy: impact of syndrome, age, and state. Epilepsia. 2009; 50: 1572\u20131578.","DOI":"10.1111\/j.1528-1167.2008.02001.x"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Benbadis SR, Beniczky S, Bertram E, MacIver S, Mosh\u00e9 SL. The role of EEG in patients with suspected epilepsy. Epileptic Disorders. 2020; 22: 143\u2013155.","DOI":"10.1684\/epd.2020.1151"},{"key":"ref14","unstructured":"Albuja AC, Ighodaro ET, Khan GQ. Absence Seizure. In. StatPearls Publishing: Treasure Island (FL), USA. 2025."},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Devinsky O, Elder C, Sivathamboo S, Scheffer IE, Koepp MJ. Idiopathic Generalized Epilepsy: Misunderstandings, Challenges, and Opportunities. Neurology. 2024; 102: e208076.","DOI":"10.1212\/WNL.0000000000208076"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Panayiotopoulos CP. The new ILAE report on terminology and concepts for the organization of epilepsies: critical review and contribution. Epilepsia. 2012; 53: 399\u2013404.","DOI":"10.1111\/j.1528-1167.2011.03381.x"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Bilo L, Pappat\u00e0 S, De Simone R, Meo R. The syndrome of absence status epilepsy: review of the literature. Epilepsy Research and Treatment. 2014; 2014: 624309.","DOI":"10.1155\/2014\/624309"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Russo E, Citraro R, Constanti A, Leo A, L\u00fcttjohann A, van Luijtelaar G, et al. Upholding WAG\/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development. Neuroscience and Biobehavioral Reviews. 2016; 71: 388\u2013408.","DOI":"10.1016\/j.neubiorev.2016.09.017"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Akman O, Demiralp T, Ates N, Onat FY. Electroencephalographic differences between WAG\/Rij and GAERS rat models of absence epilepsy. Epilepsy Research. 2010; 89: 185\u2013193.","DOI":"10.1016\/j.eplepsyres.2009.12.005"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Coenen AM, Van Luijtelaar EL. The WAG\/Rij rat model for absence epilepsy: age and sex factors. Epilepsy Research. 1987; 1: 297\u2013301.","DOI":"10.1016\/0920-1211(87)90005-2"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Marescaux C, Vergnes M. Genetic Absence Epilepsy in Rats from Strasbourg (GAERS). Italian Journal of Neurological Sciences. 1995; 16: 113\u2013118.","DOI":"10.1007\/BF02229083"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"van Luijtelaar G, van Oijen G. Establishing Drug Effects on Electrocorticographic Activity in a Genetic Absence Epilepsy Model: Advances and Pitfalls. Frontiers in Pharmacology. 2020; 11: 395.","DOI":"10.3389\/fphar.2020.00395"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Danober L, Deransart C, Depaulis A, Vergnes M, Marescaux C. Pathophysiological mechanisms of genetic absence epilepsy in the rat. Progress in Neurobiology. 1998; 55: 27\u201357.","DOI":"10.1016\/s0301-0082(97)00091-9"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Vergnes M, Marescaux C, Depaulis A. Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized non-convulsive epilepsy. Brain Research. 1990; 523: 87\u201391.","DOI":"10.1016\/0006-8993(90)91638-w"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Shaw FZ. Is spontaneous high-voltage rhythmic spike discharge in Long Evans rats an absence-like seizure activity? Journal of Neurophysiology. 2004; 91: 63\u201377.","DOI":"10.1152\/jn.00487.2003"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Kumar U, Li L, Bragin A, Engel J Jr. Spike and wave discharges and fast ripples during posttraumatic epileptogenesis. Epilepsia. 2021; 62: 1842\u20131851.","DOI":"10.1111\/epi.16958"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Depaulis A, David O, Charpier S. The genetic absence epilepsy rat from Strasbourg as a model to decipher the neuronal and network mechanisms of generalized idiopathic epilepsies. Journal of Neuroscience Methods. 2016; 260: 159\u2013174.","DOI":"10.1016\/j.jneumeth.2015.05.022"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Vergnes M, Marescaux C, Micheletti G, Reis J, Depaulis A, Rumbach L, et al. Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized non-convulsive epilepsy. Neuroscience Letters. 1982; 33: 97\u2013101.","DOI":"10.1016\/0304-3940(82)90136-7"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"van Luijtelaar EL, Coenen AM. Two types of electrocortical paroxysms in an inbred strain of rats. Neuroscience Letters. 1986; 70: 393\u2013397.","DOI":"10.1016\/0304-3940(86)90586-0"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Van Luijtelaar EL, Van der Werf SJ, Vossen JM, Coenen AM. Arousal, performance and absence seizures in rats. Electroencephalography and Clinical Neurophysiology. 1991; 79: 430\u2013434.","DOI":"10.1016\/0013-4694(91)90208-l"},{"key":"ref31","unstructured":"de Curtis M, Avanzini G. Thalamic regulation of epileptic spike and wave discharges. Functional Neurology. 1994; 9: 307\u2013326."},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Steriade M. Grouping of brain rhythms in corticothalamic systems. Neuroscience. 2006; 137: 1087\u20131106.","DOI":"10.1016\/j.neuroscience.2005.10.029"},{"key":"ref33","unstructured":"Steriade M. Neuronal Substrates of Sleep and Epilepsy. Cambridge University Press: Cambridge. 2003."},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Blumenfeld H. Cellular and network mechanisms of spike-wave seizures. Epilepsia. 2005; 46: 21\u201333.","DOI":"10.1111\/j.1528-1167.2005.00311.x"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Budde T, Pape HC, Kumar SS, Huguenard JR. Thalamic, Thalamocortical, and Corticocortical Models of Epilepsy with an Emphasis on Absence Seizures. Models of Seizures and Epilepsy (pp. 73\u201388). Academic Press: San Diego, CA.","DOI":"10.1016\/B978-012088554-1\/50009-8"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Zobeiri M, van Luijtelaar G, Budde T, Sysoev IV. The Brain Network in a Model of Thalamocortical Dysrhythmia. Brain Connectivity. 2019; 9: 273\u2013284.","DOI":"10.1089\/brain.2018.0621"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Avoli M. A brief history on the oscillating roles of thalamus and cortex in absence seizures. Epilepsia. 2012; 53: 779\u2013789.","DOI":"10.1111\/j.1528-1167.2012.03421.x"},{"key":"ref38","unstructured":"Hal\u00e1sz P, Kelemen A. New vistas and views in the concept of generalized epilepsies. Ideggyogyaszati Szemle. 2009; 62: 366\u2013380."},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Jones NC, Salzberg MR, Kumar G, Couper A, Morris MJ, O'Brien TJ. Elevated anxiety and depressive-like behavior in a rat model of genetic generalized epilepsy suggesting common causation. Experimental Neurology. 2008; 209: 254\u2013260.","DOI":"10.1016\/j.expneurol.2007.09.026"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Sarkisova K, van Luijtelaar G. The WAG\/Rij strain: a genetic animal model of absence epilepsy with comorbidity of depression [corrected]. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2011; 35: 854\u2013876.","DOI":"10.1016\/j.pnpbp.2010.11.010"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Leo A, De Caro C, Nesci V, Tallarico M, Mangano G, Palma E, et al. WAG\/Rij rat model: a resource for the pharmacology of epileptogenesis and related neurological\/psychiatric comorbidities. Neuroscience Research Notes. 2019; 1: 18\u201334.","DOI":"10.31117\/neuroscirn.v1i3.22"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Gruenbaum BF, Sandhu MRS, Bertasi RAO, Bertasi TGO, Schonwald A, Kurup A, et al. Absence seizures and their relationship to depression and anxiety: Evidence for bidirectionality. Epilepsia. 2021; 62: 1041\u20131056.","DOI":"10.1111\/epi.16862"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Sitnikova E. Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG\/Rij Rats). Biomedicines. 2024; 12: 122.","DOI":"10.3390\/biomedicines12010122"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Coenen AML, Van Luijtelaar ELJM. Genetic animal models for absence epilepsy: a review of the WAG\/Rij strain of rats. Behavior Genetics. 2003; 33: 635\u2013655.","DOI":"10.1023\/a:1026179013847"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Karson A, Utkan T, Balc\u0131 F, Ar\u0131c\u0131o\u011flu F, Ate\u015f N. Age-dependent decline in learning and memory performances of WAG\/Rij rat model of absence epilepsy. Behavioral and Brain Functions. 2012; 8: 51.","DOI":"10.1186\/1744-9081-8-51"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Lazarini-Lopes W, Campos-Rodriguez C, Palmer D, N'Gouemo P, Garcia-Cairasco N, Forcelli PA. Absence epilepsy in male and female WAG\/Rij rats: A longitudinal EEG analysis of seizure expression. Epilepsy Research. 2021; 176: 106693.","DOI":"10.1016\/j.eplepsyres.2021.106693"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Crunelli V, Cope DW, Terry JR. Transition to absence seizures and the role of GABA(A) receptors. Epilepsy Research. 2011; 97: 283\u2013289.","DOI":"10.1016\/j.eplepsyres.2011.07.011"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Paydar A, Lee B, Gangadharan G, Lee S, Hwang EM, Shin HS. Extrasynaptic GABAA receptors in mediodorsal thalamic nucleus modulate fear extinction learning. Molecular Brain. 2014; 7: 39.","DOI":"10.1186\/1756-6606-7-39"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Crunelli V, L\u0151rincz ML, McCafferty C, Lambert RC, Leresche N, Di Giovanni G, et al. Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures. Brain. 2020; 143: 2341\u20132368.","DOI":"10.1093\/brain\/awaa072"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Wong M. Too much inhibition leads to excitation in absence epilepsy. Epilepsy Currents. 2010; 10: 131\u2013132.","DOI":"10.1111\/j.1535-7511.2010.01379.x"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Cope DW, Di Giovanni G, Fyson SJ, Orb\u00e1n G, Errington AC, Lorincz ML, et al. Enhanced tonic GABAA inhibition in typical absence epilepsy. Nature Medicine. 2009; 15: 1392\u20131398.","DOI":"10.1038\/nm.2058"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Lee S, Ahmed T, Lee S, Kim H, Choi S, Kim DS, et al. Bidirectional modulation of fear extinction by mediodorsal thalamic firing in mice. Nature Neuroscience. 2012; 15: 308\u2013314.","DOI":"10.1038\/nn.2999"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Lee S, Shin HS. The role of mediodorsal thalamic nucleus in fear extinction. Journal of Analytical Science and Technology. 2016; 7: 13.","DOI":"10.1186\/s40543-016-0093-6"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Roelofs K. Freeze for action: neurobiological mechanisms in animal and human freezing. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 2017; 372: 20160206.","DOI":"10.1098\/rstb.2016.0206"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Russo AS, Parsons RG. Behavioral Expression of Contextual Fear in Male and Female Rats. Frontiers in Behavioral Neuroscience. 2021; 15: 671017.","DOI":"10.3389\/fnbeh.2021.671017"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Ball TM, Gunaydin LA. Measuring maladaptive avoidance: from animal models to clinical anxiety. Neuropsychopharmacology. 2022; 47: 978\u2013986.","DOI":"10.1038\/s41386-021-01263-4"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Sangha S, Diehl MM, Bergstrom HC, Drew MR. Know safety, no fear. Neuroscience and Biobehavioral Reviews. 2020; 108: 218\u2013230.","DOI":"10.1016\/j.neubiorev.2019.11.006"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Flandreau EI, Toth M. Animal Models of PTSD: A Critical Review. Current Topics in Behavioral Neurosciences. 2018; 38: 47\u201368.","DOI":"10.1007\/7854_2016_65"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Verbitsky A, Dopfel D, Zhang N. Rodent models of post-traumatic stress disorder: behavioral assessment. Translational Psychiatry. 2020; 10: 132.","DOI":"10.1038\/s41398-020-0806-x"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Galatzer-Levy IR, Moscarello J, Blessing EM, Klein J, Cain CK, LeDoux JE. Heterogeneity in signaled active avoidance learning: substantive and methodological relevance of diversity in instrumental defensive responses to threat cues. Frontiers in Systems Neuroscience. 2014; 8: 179.","DOI":"10.3389\/fnsys.2014.00179"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Arnegard ME, Whitten LA, Hunter C, Clayton JA. Sex as a Biological Variable: A 5-Year Progress Report and Call to Action. Journal of Women's Health (2002). 2020; 29: 858\u2013864.","DOI":"10.1089\/jwh.2019.8247"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Waltz M, Fisher JA, Lyerly AD, Walker RL. Evaluating the National Institutes of Health's Sex as a Biological Variable Policy: Conflicting Accounts from the Front Lines of Animal Research. Journal of Women's Health (2002). 2021; 30: 348\u2013354.","DOI":"10.1089\/jwh.2020.8674"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"van Haaren F, van Hest A, Heinsbroek RP. Behavioral differences between male and female rats: effects of gonadal hormones on learning and memory. Neuroscience and Biobehavioral Reviews. 1990; 14: 23\u201333.","DOI":"10.1016\/s0149-7634(05)80157-5"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Gruene TM, Flick K, Stefano A, Shea SD, Shansky RM. Sexually divergent expression of active and passive conditioned fear responses in rats. elife. 2015; 4: e11352.","DOI":"10.7554\/eLife.11352"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"Mitchell JR, Trettel SG, Li AJ, Wasielewski S, Huckleberry KA, Fanikos M, et al. Darting across space and time: parametric modulators of sex-biased conditioned fear responses. Learning & Memory. 2022; 29: 171\u2013180.","DOI":"10.1101\/lm.053587.122"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"Bangasser D. To freeze or not to freeze. ELife. 2015; 4: e13119.","DOI":"10.7554\/eLife.13119"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"Alexandrov P, Pupikina M, Adaeva Z, Sitnikova E. The Difference between Male and Female Rats in Terms of Freezing and Aversive Ultrasonic Vocalization in an Active Avoidance Test. Physiologia. 2023; 3: 406\u2013420.","DOI":"10.3390\/physiologia3030028"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"Cuomo V, Cagiano R, De Salvia MA, Mazzoccoli M, Persichella M, Renna G. Ultrasonic vocalization as an indicator of emotional state during active avoidance learning in rats. Life Sciences. 1992; 50: 1049\u20131055.","DOI":"10.1016\/0024-3205(92)90100-4"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"Diehl MM, Bravo-Rivera C, Quirk GJ. The study of active avoidance: A platform for discussion. Neuroscience and Biobehavioral Reviews. 2019; 107: 229\u2013237.","DOI":"10.1016\/j.neubiorev.2019.09.010"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"L\u00f3pez-Moraga A, Beckers T, Luyten L. The effects of stress on avoidance in rodents: An unresolved matter. Frontiers in Behavioral Neuroscience. 2022; 16: 983026.","DOI":"10.3389\/fnbeh.2022.983026"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"Bal NV, Rysakova MP, Vinarskaya AK, Ivanova V, Zuzina AB, Balaban PM. Cued memory reconsolidation in rats requires nitric oxide. The European Journal of Neuroscience. 2017; 45: 643\u2013647.","DOI":"10.1111\/ejn.13503"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"Sitnikova E, Hramov AE, Koronovsky AA, van Luijtelaar G. Sleep spindles and spike-wave discharges in EEG: Their generic features, similarities and distinctions disclosed with Fourier transform and continuous wavelet analysis. Journal of Neuroscience Methods. 2009; 180: 304\u2013316.","DOI":"10.1016\/j.jneumeth.2009.04.006"},{"key":"ref73","doi-asserted-by":"publisher","unstructured":"Sitnikova E, van Luijtelaar G. Electroencephalographic characterization of spike-wave discharges in cortex and thalamus in WAG\/Rij rats. Epilepsia. 2007; 48: 2296\u20132311.","DOI":"10.1111\/j.1528-1167.2007.01250.x"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"Sitnikova E, Smirnov K. Active avoidance learning in WAG\/Rij rats with genetic predisposition to absence epilepsy. Brain Research Bulletin. 2020; 165: 198\u2013208.","DOI":"10.1016\/j.brainresbull.2020.10.007"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"Hramov A, Koronovskii A, Makarov V, Maksimenko V, Pavlov A, Sitnikova E. Wavelets in Neuroscience. Springer International Publishing: Cham. 2021.","DOI":"10.1007\/978-3-030-75992-6"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"Sitnikova E, Pupikina M. Distinct phenotypes, shared etiology: Dissociation of absence epilepsy, audiogenic seizures, and anhedonia in a genetic rat model. Advanced Neurology. 2026; 025010133.","DOI":"10.36922\/AN025010133"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"Pupikina M, Sitnikova E. Sex Differences in Behavior and Learning Abilities in Adult Rats. Life. 2023; 13: 547.","DOI":"10.3390\/life13020547"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"Coenen AM, Drinkenburg WH, Peeters BW, Vossen JM, van Luijtelaar EL. Absence epilepsy and the level of vigilance in rats of the WAG\/Rij strain. Neuroscience and Biobehavioral Reviews. 1991; 15: 259\u2013263.","DOI":"10.1016\/s0149-7634(05)80005-3"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"Smyk MK, Sysoev IV, Sysoeva MV, van Luijtelaar G, Drinkenburg WH. Can absence seizures be predicted by vigilance states?: Advanced analysis of sleep-wake states and spike-wave discharges' occurrence in rats. Epilepsy & Behavior : E&B. 2019; 96: 200\u2013209.","DOI":"10.1016\/j.yebeh.2019.04.012"},{"key":"ref80","doi-asserted-by":"publisher","unstructured":"Smyk MK, van Luijtelaar G. Circadian Rhythms and Epilepsy: A Suitable Case for Absence Epilepsy. Frontiers in Neurology. 2020; 11: 245.","DOI":"10.3389\/fneur.2020.00245"},{"key":"ref81","doi-asserted-by":"publisher","unstructured":"Midzyanovskaya IS, Shatskova AB, Sarkisova KY, van Luijtelaar G, Tuomisto L, Kuznetsova GD. Convulsive and nonconvulsive epilepsy in rats: effects on behavioral response to novelty stress. Epilepsy & Behavior : E&B. 2005; 6: 543\u2013551.","DOI":"10.1016\/j.yebeh.2005.03.005"},{"key":"ref82","doi-asserted-by":"publisher","unstructured":"Huguenard J. Current Controversy: Spikes, Bursts, and Synchrony in Generalized Absence Epilepsy: Unresolved Questions Regarding Thalamocortical Synchrony in Absence Epilepsy. Epilepsy Currents. 2019; 19: 105\u2013111.","DOI":"10.1177\/1535759719835355"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"Osterhagen L, Breteler M, van Luijtelaar G. Does arousal interfere with operant conditioning of spike-wave discharges in genetic epileptic rats? Epilepsy Research. 2010; 90: 75\u201382.","DOI":"10.1016\/j.eplepsyres.2010.03.010"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"Taylor JA, Rodgers KM, Bercum FM, Booth CJ, Dudek FE, Barth DS. Voluntary Control of Epileptiform Spike-Wave Discharges in Awake Rats. The Journal of Neuroscience. 2017; 37: 5861\u20135869.","DOI":"10.1523\/JNEUROSCI.3235-16.2017"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"Ewell LA. Assessing Levels of Awareness During Seizures in Animal Models. Epilepsy Currents. 2017; 17: 372\u2013373.","DOI":"10.5698\/1535-7597.17.6.372"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"Shanazz K, Dixon-Melvin R, Nalloor R, Thumar R, Vazdarjanova AI. Sex Differences In Avoidance Extinction After Contextual Fear Conditioning: Anxioescapic Behavior In Female Rats. Neuroscience. 2022; 497: 146\u2013156.","DOI":"10.1016\/j.neuroscience.2022.06.031"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. Journal of Traumatic Stress. 2013; 26: 537\u2013547.","DOI":"10.1002\/jts.21848"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"Hsu CMK, Kleim B, Nicholson EL, Zuj DV, Cushing PJ, Gray KE, et al. Sex differences in intrusive memories following trauma. PloS One. 2018; 13: e0208575.","DOI":"10.1371\/journal.pone.0208575"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"Stein MB, Walker JR, Hazen AL, Forde DR. Full and partial posttraumatic stress disorder: findings from a community survey. The American Journal of Psychiatry. 1997; 154: 1114\u20131119.","DOI":"10.1176\/ajp.154.8.1114"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"Walf AA, Frye CA. Estradiol decreases anxiety behavior and enhances inhibitory avoidance and gestational stress produces opposite effects. Stress. 2007; 10: 251\u2013260.","DOI":"10.1080\/00958970701220416"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"Louvart H, Maccari S, Lesage J, L\u00e9onhardt M, Dickes-Coopman A, Darnaud\u00e9ry M. Effects of a single footshock followed by situational reminders on HPA axis and behaviour in the aversive context in male and female rats. Psychoneuroendocrinology. 2006; 31: 92\u201399.","DOI":"10.1016\/j.psyneuen.2005.05.014"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"Beckers T, Krypotos AM, Boddez Y, Effting M, Kindt M. What's wrong with fear conditioning? Biological Psychology. 2013; 92: 90\u201396.","DOI":"10.1016\/j.biopsycho.2011.12.015"},{"key":"ref93","doi-asserted-by":"publisher","unstructured":"Day HLL, Stevenson CW. The neurobiological basis of sex differences in learned fear and its inhibition. The European Journal of Neuroscience. 2020; 52: 2466\u20132486.","DOI":"10.1111\/ejn.14602"},{"key":"ref94","doi-asserted-by":"publisher","unstructured":"Avcu P, Jiao X, Myers CE, Beck KD, Pang KCH, Servatius RJ. Avoidance as expectancy in rats: sex and strain differences in acquisition. Frontiers in Behavioral Neuroscience. 2014; 8: 334.","DOI":"10.3389\/fnbeh.2014.00334"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"van Luijtelaar G, Onat FY, Gallagher MJ. Animal models of absence epilepsies: what do they model and do sex and sex hormones matter? Neurobiology of Disease. 2014; 72: 167\u2013179.","DOI":"10.1016\/j.nbd.2014.08.014"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"Rosales VP, Ikeda K, Hizaki K, Naruo T, Nozoe SI, Ito G. Emotional stress and brux-like activity of the masseter muscle in rats. European Journal of Orthodontics. 2002; 24: 107\u2013117.","DOI":"10.1093\/ejo\/24.1.107"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/9\/10.31083\/JIN52427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:17:19Z","timestamp":1790698639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/9\/10.31083\/JIN52427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":96,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"alternative-id":["S0219-6352(26)01177-0"],"URL":"https:\/\/doi.org\/10.31083\/jin52427","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"article-number":"52427"}}