{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T01:14:25Z","timestamp":1768094065572,"version":"3.49.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Anxiety and anxiety-influenced disorders are sexually dimorphic with women being disproportionately affected compared to men. Given the increased prevalence in women and the documented differences in anxiety and trauma behavior between male and female rats this paper sought to examine the link between stress, anxiety, and fear learning and extinction in female rats. We tested the hypothesis that a mild stressor will induce short-and long-term increases in anxiety and produce long term effects on subsequent fear learning and extinction behavior.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We induced anxiety in female Sprague\u2013 Dawley rats with a short (3 min) exposure to a ball of cat hair infused with 150 \u03bcl of cat urine (mild stressor) that elicits innate fear but does not cause fear conditioning. The control group was exposed to fake cat hair. Anxiety was assessed in the Light-Dark Open Field (LDOF) or Elevated Plus Maze (EPM) before, immediately after and 4 days after stimulus exposure. Two weeks later, all animals were subject to Contextual Fear Conditioning (CFC) in the Shock Arm of a Y-maze, blocked off from the rest of the maze. Memory and fear extinction (learning of safety) was assessed in the following four days by placing each rat in one of the Safe Arms and measuring avoidance extinction (time spent and number of entries in the Shock Arm).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cat hair exposure induced changes in anxiety-like behavior in the short-term that appeared resolved 4 days later. However, the cat-hair exposed rats had long-term (2 weeks) phenotypic changes expressed as altered exploratory behavior in an emotionally neutral novel place. Fear learning and extinction were not impaired. Yet, using avoidance extinction, we demonstrated that the phenotypic difference induced by the mild stressor could be documented and dissociated from learning and memory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings demonstrate that the history of stress, even mild stress, has subtle long-term effects on behavior even when short-term anxiety appears resolved.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnbeh.2023.1231563","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T08:37:40Z","timestamp":1693816660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A mild stressor induces short-term anxiety and long-term phenotypic changes in trauma-related behavior in female rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Khadijah","family":"Shanazz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Nalloor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Almira","family":"Vazdarjanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/0031-9384(93)90050-P","article-title":"Lasting effects on rodent anxiety of a single exposure to a cat","volume":"54","author":"Adamec","year":"1993","journal-title":"Physiol. Behav."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e8887727","DOI":"10.1155\/2020\/8887727","article-title":"Prevalence and predictors of depression, anxiety, and stress among youth at the time of COVID-19: an online Cross-sectional multicountry study","volume":"2020","author":"Al Omari","year":"2020","journal-title":"Depress. Res. Treat."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3389\/fnsys.2019.00085","article-title":"Investigating individual pre-trauma susceptibility to a PTSD-like phenotype in animals","volume":"13","author":"Alexander","year":"2020","journal-title":"Front. Syst. Neurosci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e0247679","DOI":"10.1371\/journal.pone.0247679","article-title":"Anxiety, depression, stress, fear and social support during COVID-19 pandemic among Jordanian healthcare workers","volume":"16","author":"Alnazly","year":"2021","journal-title":"PLoS One"},{"key":"ref5","volume-title":"Diagnostic and Statistical Manual of Mental Disorders (DSM-4)","year":"2000"},{"key":"ref6","volume-title":"Diagnostic and Statistical Manual of Mental Disorders (DSM-5\u00ae)","year":"2013"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1017\/S1461145704004808","article-title":"Exposure to juvenile stress exacerbates the behavioural consequences of exposure to stress in the adult rat","volume":"8","author":"Avital","year":"2005","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"327","DOI":"10.31887\/DCNS.2015.17.3\/bbandelow","article-title":"Epidemiology of anxiety disorders in the 21st century","volume":"17","author":"Bandelow","year":"2015","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"93","DOI":"10.31887\/DCNS.2017.19.2\/bbandelow","article-title":"Treatment of anxiety disorders","volume":"19","author":"Bandelow","year":"2017","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/s41583-021-00513-0","article-title":"Sex differences in anxiety and depression: circuits and mechanisms","volume":"22","author":"Bangasser","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1080\/08995605.2020.1754123","article-title":"PTSD relapse in veterans of Iraq and Afghanistan: a systematic review","volume":"32","author":"Berge","year":"2020","journal-title":"Mil. Psychol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1037\/0735-7036.103.1.70","article-title":"Antipredator defensive behaviors in a visible burrow system","volume":"103","author":"Blanchard","year":"1989","journal-title":"J. Comp. Psychol."},{"key":"ref13","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/978-94-009-2403-1_7","article-title":"An ethoexperimental approach to the study of defense","volume-title":"Ethoexperimental Approaches to the Study of Behavior","author":"Blanchard","year":"1989"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1037\/0735-7036.100.2.101","article-title":"Defensive behavior of laboratory and wild Rattus norvegicus","volume":"100","author":"Blanchard","year":"1986","journal-title":"J. Comp. Psychol."},{"key":"ref15","first-page":"268","article-title":"Evaluation of psychiatric disability in PTSD of military origin","volume":"41","author":"Bleich","year":"2004","journal-title":"Isr. J. Psychiatry Relat. Sci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1017\/S0033291799008612","article-title":"Vulnerability to assaultive violence: further specification of the sex difference in post-traumatic stress disorder","volume":"29","author":"Breslau","year":"1999","journal-title":"Psychol. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/1471-2458-6-114","article-title":"Mental health: a cause or consequence of injury? A population-based matched cohort study","volume":"6","author":"Cameron","year":"2006","journal-title":"BMC Public Health"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/(SICI)1099-1700(199807)14:3<143::AID-SMI770>3.0.CO;2-S","article-title":"Disaster-related post-traumatic stress in police officers: a field study of the impact of debriefing","volume":"14","author":"Carlier","year":"1998","journal-title":"Stress Medicine"},{"key":"ref19","doi-asserted-by":"crossref","DOI":"10.5772\/28363","article-title":"Sex differences in PTSD","volume-title":"Post Traumatic Stress Disorders in a Global Context","author":"Christiansen","year":"2012"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1016\/j.biopsych.2005.12.003","article-title":"Blunted HPA Axis response to stress influences susceptibility to posttraumatic stress response in rats","volume":"59","author":"Cohen","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nrdp.2017.24","article-title":"Anxiety disorders","volume":"3","author":"Craske","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0163-7258(90)90084-F","article-title":"Animal models of anxiety based on classical conditioning: the conditioned emotional response (CER) and the fear-potentiated startle effect","volume":"47","author":"Davis","year":"1990","journal-title":"Pharmacol. Ther."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S0149-7634(01)00044-6","article-title":"Defensive behavior in rats towards predatory odors: a review","volume":"25","author":"Dielenberg","year":"2001","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"107562","DOI":"10.1016\/j.nlm.2021.107562","article-title":"Emotional state alters encoding of long-term spatial episodic memory","volume":"187","author":"Dixon-Melvin","year":"2022","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.cobeha.2018.03.013","article-title":"When planning to survive goes wrong: predicting the future and replaying the past in anxiety and PTSD","volume":"24","author":"Gagne","year":"2018","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1002\/dev.21313","article-title":"Fear conditioned responses and PTSD symptoms in children: sex differences in fear-related symptoms","volume":"57","author":"Gamwell","year":"2015","journal-title":"Dev. Psychobiol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.genhosppsych.2009.05.003","article-title":"Trauma exposure and stress-related disorders in inner city primary care patients","volume":"31","author":"Gillespie","year":"2009","journal-title":"Gen. Hosp. Psychiatry"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1523\/JNEUROSCI.17-04-01505.1997","article-title":"A five minute experience in the elevated plus-maze alters the state of the benzodiazepine receptor in the dorsal raphe nucleus","volume":"17","author":"Gonzalez","year":"1997","journal-title":"J. Neurosci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.bbr.2012.10.014","article-title":"Comparison between low doses of TMT and cat odor exposure in anxiety-and fear-related behaviors in mice","volume":"238","author":"Hacquemand","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/0091-3057(95)02126-4","article-title":"A review of the validity and variability of the elevated plus-maze as an animal model of anxiety","volume":"54","author":"Hogg","year":"1996","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1152\/physrev.00018.2015","article-title":"Fear memory","volume":"96","author":"Izquierdo","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"012","DOI":"10.24966\/PDA-0150\/100012","article-title":"Sex differences in anxiety disorders: a review","volume":"4","author":"Jalnapurkar","year":"2018","journal-title":"J Psychiatry Depress. Anxiety"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.24017\/covid.5","article-title":"Depression, anxiety, and stress in the time of COVID-19 pandemic in Kurdistan region, Iraq","author":"Kamal","year":"2020","journal-title":"Kurdistan J. Appl. Res."},{"key":"ref34","first-page":"981","article-title":"Chapter 67 in Neuropsychopharmacology the 5th Generation of Progress","author":"Kessler","year":"2002","journal-title":"American College of Neuropsychopharmacology"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1001\/archpsyc.1995.03950240066012","article-title":"Posttraumatic stress disorder in the National Comorbidity Survey","volume":"52","author":"Kessler","year":"1995","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3109\/10253899909001110","article-title":"Fear-potentiation in the elevated plus-maze test depends on stressor controllability and fear conditioning","volume":"3","author":"Korte","year":"1999","journal-title":"Stress"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1055\/s-0040-1716442","article-title":"Prevalence of depression, anxiety, and stress during COVID-19 pandemic","volume":"11","author":"Lakhan","year":"2020","journal-title":"J. Neurosci. Rural Pract."},{"key":"ref38","first-page":"21","article-title":"The effects of yoga on anxiety and stress","volume":"17","author":"Li","year":"2012","journal-title":"Altern. Med. Rev."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.yhbeh.2015.04.002","article-title":"Sex differences in anxiety disorders: interactions between fear, stress, and gonadal hormones","volume":"76","author":"Maeng","year":"2015","journal-title":"Horm. Behav."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1196\/annals.1364.001","article-title":"Predictors of posttraumatic stress in police and other first responders","volume":"1071","author":"Marmar","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1136\/emj.19.5.400","article-title":"The psychological burden of injury: an 18 month prospective cohort study","volume":"19","author":"Mason","year":"2002","journal-title":"Emerg. Med. J."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"4134","DOI":"10.1523\/JNEUROSCI.0187-04.2004","article-title":"Neural correlates of cat odor-induced anxiety in rats: region-specific effects of the benzodiazepine midazolam","volume":"24","author":"McGregor","year":"2004","journal-title":"J. Neurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0014-2999(03)01279-2","article-title":"A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze","volume":"463","author":"Mechiel Korte","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref44","author":"Mitchell","year":"2022"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.yhbeh.2009.08.002","article-title":"Cat odor causes long-lasting contextual fear conditioning and increased pituitary-adrenal activation, without modifying anxiety","volume":"56","author":"Mu\u00f1oz-Abell\u00e1n","year":"2009","journal-title":"Horm. Behav."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e19760","DOI":"10.1371\/journal.pone.0019760","article-title":"Predicting impaired extinction of traumatic memory and elevated startle","volume":"6","author":"Nalloor","year":"2011","journal-title":"PLoS One"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.nlm.2014.02.006","article-title":"Altered hippocampal function before emotional trauma in rats susceptible to PTSD-like behaviors","volume":"112","author":"Nalloor","year":"2014","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0165-0270(85)90031-7","article-title":"Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat","volume":"14","author":"Pellow","year":"1985","journal-title":"J. Neurosci. Methods"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1002\/jts.22035","article-title":"The strongest correlates of PTSD for firefighters: number, Recency, frequency, or perceived threat of traumatic events?","volume":"28","author":"Pinto","year":"2015","journal-title":"J. Trauma. Stress."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0166-4328(96)00164-7","article-title":"A multiple-test study of anxiety-related behaviours in six inbred rat strains","volume":"85","author":"Ramos","year":"1997","journal-title":"Behav. Brain Res."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1177\/070674371405900902","article-title":"Posttraumatic stress disorder in adults: impact, comorbidity, risk factors, and treatment","volume":"59","author":"Sareen","year":"2014","journal-title":"Can. J. Psychiatr."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"11112","DOI":"10.1038\/s41598-020-68008-z","article-title":"Trait and state anxiety are mapped differently in the human brain","volume":"10","author":"Saviola","year":"2020","journal-title":"Sci. Rep."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s10597-020-00728-y","article-title":"Prevalence, psychological responses and associated correlates of depression, anxiety and stress in a global population, during the coronavirus disease (COVID-19) pandemic","volume":"57","author":"Shah","year":"2021","journal-title":"Community Ment. Health J."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/wps.20608","article-title":"Estimating the risk of PTSD in recent trauma survivors: results of the international consortium to predict PTSD (ICPP)","volume":"18","author":"Shalev","year":"2019","journal-title":"World Psychiatry"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.ajp.2013.01.014","article-title":"Correlates of depression, anxiety and stress among Malaysian university students","volume":"6","author":"Shamsuddin","year":"2013","journal-title":"Asian J. Psychiatr."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"109325","DOI":"10.1016\/j.jneumeth.2021.109325","article-title":"Light-dark open field (LDOF): a novel task for sensitive assessment of anxiety","volume":"363","author":"Shanazz","year":"2021","journal-title":"J. Neurosci. Methods"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.neuroscience.2022.06.031","article-title":"Sex differences in avoidance extinction after contextual fear conditioning: Anxioescapic behavior in female rats","volume":"497","author":"Shanazz","year":"2022","journal-title":"Neuroscience"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.chiabu.2014.01.017","article-title":"Comorbidity of PTSD in anxiety and depressive disorders: prevalence and shared risk factors","volume":"38","author":"Spinhoven","year":"2014","journal-title":"Child Abuse Negl."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"495","DOI":"10.31887\/DCNS.2011.13.4\/tsteimer","article-title":"Animal models of anxiety disorders in rats and mice: some conceptual issues","volume":"13","author":"Steimer","year":"2011","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1046\/j.0953-816x.2001.01696.x","article-title":"Disrupting basolateral amygdala function impairs unconditioned freezing and avoidance in rats","volume":"14","author":"Vazdarjanova","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref61","first-page":"15003","article-title":"Basolateral amygdala infusions of lidocaine disrupt both acquisition and consolidation of memory for contextual fear conditioning","volume":"24","author":"Vazdarjanova","year":"1998","journal-title":"Soc. Neurosci. Abstr."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/dev.21060","article-title":"Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long-term enhancement of adult defensive behaviors","volume":"55","author":"Wright","year":"2013","journal-title":"Dev. 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