{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:20:51Z","timestamp":1793420451500,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-15-00301"],"award-info":[{"award-number":["24-15-00301"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic stress alters hypothalamic\u2013pituitary\u2013adrenal (HPA) axis function, affecting corticosterone regulation and adaptive responses. Understanding individual variability in stress adaptation requires identifying distinct HPA axis response patterns. Here, we assessed HPA axis sensitivity in male C57BL6 mice exposed to 30 days of chronic social defeat stress (CSDS). Negative feedback integrity was evaluated using the dexamethasone suppression test (DST), with corticosterone measured after saline or low-dose dexamethasone administration at days 10 and 30. Behavioral testing (open field, elevated plus maze, social interaction test, partition, social defeat, forced swimming test, sucrose preference test) and qPCR analysis of HPA-axis-related genes in the hypothalamus (Crh, Crhr1, Crhbp, Fkbp5, Nr3c1), pituitary (Pomc, Crhr1, Nr3c1, Nr3c2), and adrenal glands (Cyp11a1, Cyp11b1, Hsd11b1, Mc2r, Star, Fkbp5, Nr3c1) were performed. K-means cluster analysis identified three distinct response profiles differing in baseline and dexamethasone-suppressed corticosterone levels. Clusters also exhibited differences in behavioral phenotypes and HPA axis gene expression. Cluster 1 showed low basal corticosterone and an abnormal dexamethasone suppression response, without significant Crh or Crhbp dysregulation in the hypothalamus. Cluster 2 exhibited elevated basal corticosterone, a blunted dexamethasone response, anhedonia, and reduced immobility in the forced swim test; increased Crh and reduced Fkbp5 suggested enhanced glucocorticoid receptor sensitivity and sustained hypercortisolemia. Cluster 3, characterized by normal basal corticosterone and normal dexamethasone response, displayed upregulation of Crh and Crhbp, consistent with balanced and potentially adaptive HPA axis regulation under chronic stress. These results demonstrate that corticosterone response heterogeneity reflects distinct adaptive trajectories under chronic stress. Identifying behavioral and molecular markers of these strategies may advance understanding of stress vulnerability and resilience mechanisms, with implications for stress-related disorders.<\/jats:p>","DOI":"10.3390\/ijms262311436","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:43:22Z","timestamp":1764157402000},"page":"11436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chronic Stress Segregates Mice into Distinct Behavioral Phenotypes Based on Glucocorticoid Sensitivity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-7031","authenticated-orcid":false,"given":"Polina","family":"Ritter","sequence":"first","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, Pirogova Street 2, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5164-6264","authenticated-orcid":false,"given":"Rasha","family":"Salman","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8979-2857","authenticated-orcid":false,"given":"Yuliya","family":"Ryabushkina","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5602-5149","authenticated-orcid":false,"given":"Natalya","family":"Bondar","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, Pirogova Street 2, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41380-021-01224-9","article-title":"The Neuroendocrinology of Stress: The Stress-Related Continuum of Chronic Disease Development","volume":"27","author":"Agorastos","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.iac.2009.02.006","article-title":"Social Interactions, Stress, and Immunity","volume":"29","author":"Avitsur","year":"2009","journal-title":"Immunol. Allergy Clin. North Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0165-0327(00)00352-9","article-title":"Stress, Hypercortisolism and Corticosteroid Receptors in Depression: Implications for Therapy","volume":"62","author":"Holsboer","year":"2001","journal-title":"J. Affect. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.biopsych.2014.07.036","article-title":"Enhancement of Stress Resilience Through Histone Deacetylase 6\u2013Mediated Regulation of Glucocorticoid Receptor Chaperone Dynamics","volume":"77","author":"Jochems","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S0165-5728(01)00273-9","article-title":"Social Stress Increases the Susceptibility to Endotoxic Shock","volume":"115","author":"Quan","year":"2001","journal-title":"J. Neuroimmunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.5127\/pr.034413","article-title":"The HPA Axis in the Pathogenesis and Treatment of Depressive Disorders: Integrating Clinical and Molecular Findings","volume":"a3","author":"Baumeister","year":"2016","journal-title":"Psychopathol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1007\/s12035-017-0586-3","article-title":"Molecular Adaptations to Social Defeat Stress and Induced Depression in Mice","volume":"55","author":"Bondar","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1159\/000506484","article-title":"Alterations of the HPA Axis Observed in Patients with Major Depressive Disorder and Their Relation to Early Life Stress: A Systematic Review","volume":"79","author":"Ceruso","year":"2020","journal-title":"Neuropsychobiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neubiorev.2020.01.011","article-title":"The Contagion of Social Defeat Stress: Insights from Rodent Studies","volume":"111","author":"Carnevali","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.psyneuen.2007.02.011","article-title":"Persistent Neuroendocrine and Behavioral Effects of a Novel, Etiologically Relevant Mouse Paradigm for Chronic Social Stress during Adolescence","volume":"32","author":"Schmidt","year":"2007","journal-title":"Psychoneuroendocrinology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0018-506X(02)00011-9","article-title":"Facilitation of Hypothalamic\u2013Pituitary\u2013Adrenal Responses to Novel Stress Following Repeated Social Stress Using the Resident\/Intruder Paradigm","volume":"43","author":"Bhatnagar","year":"2003","journal-title":"Horm. Behav."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0306-4530(98)00050-X","article-title":"Housing Familiar Male Wildtype Rats Together Reduces the Long-Term Adverse Behavioural and Physiological Effects of Social Defeat","volume":"24","author":"Ruis","year":"1999","journal-title":"Psychoneuroendocrinology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.psyneuen.2003.08.003","article-title":"Behavioral and Physiological Characterization of Male Mice under Chronic Psychosocial Stress","volume":"29","author":"Bartolomucci","year":"2004","journal-title":"Psychoneuroendocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1176\/ajp.154.11.1497","article-title":"DST Studies in Psychotic Depression: A Meta-Analysis","volume":"154","author":"Nelson","year":"1997","journal-title":"Am. J. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1600-0447.1980.tb00576.x","article-title":"Resistance to Inhibiting Effect of Dexamethasone in Patients with Endogenous Depression","volume":"61","author":"Nuller","year":"1980","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1097\/PSY.0b013e31820ad12b","article-title":"Depression and Hypothalamic-Pituitary-Adrenal Activation: A Quantitative Summary of Four Decades of Research","volume":"73","author":"Stetler","year":"2011","journal-title":"Psychosom. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1159\/000125388","article-title":"Decreased Sensitivity to Glucocorticoid Fast Feedback in Chronically Stressed Rats","volume":"51","author":"Young","year":"1990","journal-title":"Neuroendocrinology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuroscience.2014.11.035","article-title":"Behavioral and Molecular Alterations in Mice Resulting from Chronic Treatment with Dexamethasone: Relevance to Depression","volume":"286","author":"Skupio","year":"2015","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.bbrc.2021.05.064","article-title":"Differential Mechanisms of Synaptic Plasticity for Susceptibility and Resilience to Chronic Social Defeat Stress in Male Mice","volume":"562","author":"Lee","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.bbr.2019.01.057","article-title":"Ketamine Improved Depressive-like Behaviors via Hippocampal Glucocorticoid Receptor in Chronic Stress Induced- Susceptible Mice","volume":"364","author":"Wang","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1037\/bne0000418","article-title":"Chronic Social Defeat Stress Mouse Model: Current View on Its Behavioral Deficits and Modifications","volume":"135","author":"Wang","year":"2021","journal-title":"Behav. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Han, Q.-Q., Yang, L., Huang, H.-J., Wang, Y.-L., Yu, R., Wang, J., Pilot, A., Wu, G.-C., Liu, Q., and Yu, J. (2017). Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00287"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"jkad114","DOI":"10.1093\/g3journal\/jkad114","article-title":"Social Defeat Stress Induces Genome-Wide 5mC and 5hmC Alterations in the Mouse Brain","volume":"13","author":"Kuehner","year":"2023","journal-title":"G3 Genes Genomes Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"O\u2019Toole, N., Zhang, T.-Y., Wen, X., Diorio, J., Silveira, P.P., Labont\u00e9, B., Nestler, E.J., and Meaney, M.J. (2019). Epigenetic Signatures of Chronic Social Stress in Stress-Susceptible Animals. bioRxiv.","DOI":"10.1101\/690826"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.coisb.2017.11.009","article-title":"Robustness, Accuracy, and Cell State Heterogeneity in Biological Systems","volume":"8","author":"Wollman","year":"2018","journal-title":"Curr. Opin. Syst. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3233\/JAD-2012-121438","article-title":"3xTg-AD Mice Exhibit an Activated Central Stress Axis During Early-Stage Pathology","volume":"33","author":"Simmons","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1210\/en.2017-03176","article-title":"Enhanced Hypothalamic NMDA Receptor Activity Contributes to Hyperactivity of HPA Axis in Chronic Stress in Male Rats","volume":"159","author":"Zhou","year":"2018","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12","DOI":"10.9758\/cpn.2021.19.1.12","article-title":"Biomarkers of Major Depressive Disorder: Knowing Is Half the Battle","volume":"19","author":"Malik","year":"2021","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1023\/A:1023411217051","article-title":"Use of the \u201cPartition\u201d Test in Behavioral and Pharmacological Experiments","volume":"33","author":"Kudryavtseva","year":"2003","journal-title":"Neurosci. Behav. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00213-012-2754-5","article-title":"Chronic Social Defeat Stress Model: Behavioral Features, Antidepressant Action, and Interaction with Biological Risk Factors","volume":"224","author":"Venzala","year":"2012","journal-title":"Psychopharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eabe4497","DOI":"10.1126\/sciadv.abe4497","article-title":"Single-Cell Molecular Profiling of All Three Components of the HPA Axis Reveals Adrenal ABCB1 as a Regulator of Stress Adaptation","volume":"7","author":"Lopez","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_32","first-page":"1130989","article-title":"Chronic Stress, Neuroinflammation, and Depression: An Overview of Pathophysiological Mechanisms and Emerging Anti-Inflammatories. Front","volume":"14","author":"Hassamal","year":"2023","journal-title":"Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nandam, L.S., Brazel, M., Zhou, M., and Jhaveri, D.J. (2020). Cortisol and Major Depressive Disorder\u2014Translating Findings From Humans to Animal Models and Back. Front. Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00974"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1046\/j.1365-2826.1999.00350.x","article-title":"Long-Lasting Deficient Dexamethasone Suppression of Hypothalamic-Pituitary-Adrenocortical Activation Following Peripheral CRF Challenge in Socially Defeated Rats","volume":"11","author":"Buwalda","year":"1999","journal-title":"J. Neuroendocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105286","DOI":"10.1016\/j.psyneuen.2021.105286","article-title":"Effects of Weariness of Life, Suicide Ideations and Suicide Attempt on HPA Axis Regulation in Depression","volume":"131","author":"Hennings","year":"2021","journal-title":"Psychoneuroendocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jad.2007.06.008","article-title":"ROC Analysis of Dexamethasone Suppression Test Threshold in Suicide Prediction after Attempted Suicide","volume":"106","author":"Jokinen","year":"2008","journal-title":"J. Affect. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jad.2017.09.052","article-title":"Atypical Depression and Non-Atypical Depression: Is HPA Axis Function a Biomarker? A Systematic Review","volume":"233","author":"Juruena","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0006-3223(92)90262-X","article-title":"Cortisol, Thyroid Hormone, and Mood in Atypical Depression: A Longitudinal Case Study","volume":"31","author":"Geracioti","year":"1992","journal-title":"Biol. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cpr.2016.09.003","article-title":"Atypical Reactivity of Heart Rate Variability to Stress and Depression across Development: Systematic Review of the Literature and Directions for Future Research","volume":"50","author":"Hamilton","year":"2016","journal-title":"Clin. Psychol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1017\/S0033291719001004","article-title":"Characteristics, Comorbidities, and Correlates of Atypical Depression: Evidence from the UK Biobank Mental Health Survey","volume":"50","author":"Brailean","year":"2020","journal-title":"Psychol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1177\/0004867417721020","article-title":"Is Atypical Depression Simply a Typical Depression with Unusual Symptoms?","volume":"51","author":"Lyndon","year":"2017","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000353620","article-title":"Coping with Chronic Social Stress in Mice: Hypothalamic-Pituitary-Adrenal\/ Sympathetic-Adrenal-Medullary Axis Activity, Behavioral Changes and Effects of Antalarmin Treatment: Implications for the Study of Stress-Related Psychopathologies","volume":"98","author":"Arregi","year":"2013","journal-title":"Neuroendocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pascual-Ahuir, A., Fita-Torr\u00f3, J., and Proft, M. (2020). Capturing and Understanding the Dynamics and Heterogeneity of Gene Expression in the Living Cell. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218278"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"You, S.-T., Jhou, Y.-T., Kao, C.-F., and Leu, J.-Y. (2019). Experimental Evolution Reveals a General Role for the Methyltransferase Hmt1 in Noise Buffering. PLoS Biol., 17.","DOI":"10.1101\/714949"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/s41592-018-0224-7","article-title":"Comparing Phenotypic Variation between Inbred and Outbred Mice","volume":"15","author":"Tuttle","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sabbagh, J.J., O\u2019Leary, J.C., Blair, L.J., Klengel, T., Nordhues, B.A., Fontaine, S.N., Binder, E.B., and Dickey, C.A. (2014). Age-Associated Epigenetic Upregulation of the FKBP5 Gene Selectively Impairs Stress Resiliency. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107241"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1891\/EMDR-2023-0019","article-title":"Transcriptional Modulation of Stress-Related Genes in Association with Early Life Stress Exposure and Trauma-Focused Psychotherapy in Treatment-Resistant Depression Patients","volume":"17","author":"Silva","year":"2023","journal-title":"J. EMDR Pract. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100356","DOI":"10.1016\/j.coemr.2022.100356","article-title":"Cause or Consequence? Understanding the Role of Cortisol in the Increased Inflammation Observed in Depression","volume":"24","author":"Sforzini","year":"2022","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/bcp.12637","article-title":"Inhaled Corticosteroids: Potency, Dose Equivalence and Therapeutic Index","volume":"80","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1210\/en.2005-0501","article-title":"Low Doses of Dexamethasone Can Produce a Hypocorticosteroid State in the Brain","volume":"146","author":"Karssen","year":"2005","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0091-3057(91)90284-9","article-title":"Social Model of Depression in Mice of C57BL\/6J Strain","volume":"38","author":"Kudryavtseva","year":"1991","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_52","first-page":"1454","article-title":"Choice of \u201ccontrol\u201d in experimental researches of animal social interactions in mice","volume":"91","author":"Avgustinovich","year":"2005","journal-title":"Ross. Fiziol. Zh. Im. IM Sechenova"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/nprot.2007.44","article-title":"The Use of the Elevated plus Maze as an Assay of Anxiety-Related Behavior in Rodents","volume":"2","author":"Walf","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0014-2999(03)01273-1","article-title":"A Review of 25 Years of the Social Interaction Test","volume":"463","author":"File","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/266730a0","article-title":"Depression: A New Animal Model Sensitive to Antidepressant Treatments","volume":"266","author":"Porsolt","year":"1977","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/BF00187257","article-title":"Reduction of Sucrose Preference by Chronic Unpredictable Mild Stress, and Its Restoration by a Tricyclic Antidepressant","volume":"93","author":"Willner","year":"1987","journal-title":"Psychopharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/2041-210X.12584","article-title":"BORIS: A Free, Versatile Open-source Event-logging Software for Video\/Audio Coding and Live Observations","volume":"7","author":"Friard","year":"2016","journal-title":"Methods Ecol. Evol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s11055-015-0142-4","article-title":"Automatic Measurement of Spatial Learning Characteristics in Mice in an Underlit Morris Water Maze","volume":"45","author":"Khotskin","year":"2015","journal-title":"Neurosci. Behav. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:46:27Z","timestamp":1764157587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":58,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311436"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311436","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}