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The interest in better understanding the role of environment on behavior and physiology led to the development of animal models of environmental manipulations. Environmental enrichment (EE), an environmental condition that allows cognitive and sensory stimulation as well as social interaction, improves cognitive function, reduces anxiety and depressive\u2010like behavior and promotes neuroplasticity. In addition, it exerts protection against neurodegenerative disorders, cognitive aging and deficits aggravated by stressful experiences. Given the beneficial effects of EE on the brain and behavior, preclinical studies have focused on its protective role as an alternative, non\u2010invasive manipulation, to help an organism to cope better with stress. A valid, reliable and effective animal model of chronic stress that enhances anxiety and depression\u2010like behavior is the chronic unpredictable mild stress (CUMS). The variety of stressors and the unpredictability in the time and sequence of exposure to prevent habituation, render CUMS an ethologically relevant model. CUMS has been associated with dysregulation of the hypothalamic\u2013pituitary\u2013adrenal axis, elevation in the basal levels of stress hormones, reduction in brain volume, dendritic atrophy and alterations in markers of synaptic plasticity. Although numerous studies have underlined the compensatory role of EE against the negative effects of various chronic stress regimens (e.g. restraint and social isolation), research concerning the interaction between EE and CUMS is sparse. The purpose of the current systematic review is to present up\u2010to\u2010date research findings regarding the protective role of EE against the negative effects of CUMS.<\/jats:p>","DOI":"10.1111\/ejn.16089","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T02:39:37Z","timestamp":1689647977000},"page":"3003-3025","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["\u03a4he neuroprotective role of environmental enrichment against behavioral, morphological, neuroendocrine and molecular changes following chronic unpredictable mild stress: A systematic review"],"prefix":"10.1111","volume":"58","author":[{"given":"\u0395vgenia","family":"Dandi","sequence":"first","affiliation":[{"name":"Laboratory of Cognitive Neuroscience, School of Psychology Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Spandou","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Physiology, School of Medicine Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7528-0487","authenticated-orcid":false,"given":"Christina","family":"Dalla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5563-4017","authenticated-orcid":false,"given":"Despina \u0391.","family":"Tata","sequence":"additional","affiliation":[{"name":"Laboratory of Cognitive Neuroscience, School of Psychology Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-042"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1749-6632.1995.TB44679.X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.07.155"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/MP.2015.142"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2020.110035"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2014.05.004"},{"key":"e_1_2_10_8_1","series-title":"Neuroscience and Biobehavioral Reviews","first-page":"101","volume-title":"Chronic unpredictable mild stress for modeling depression in rodents: Meta\u2010analysis of model reliability","author":"Antoniuk S.","year":"2019"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPM-2021-0323\/ASSET\/GRAPHIC\/J_JPM-2021-0323_FIG_004.JPG"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/JAPPLPHYSIOL.00569.2012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPHAR.2021.174578"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-019-05408-8"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.08.054"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-32-9721-0_11"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.002"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23992"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2005.01335.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062226"},{"issue":"2","key":"e_1_2_10_19_1","first-page":"127","article-title":"The life and work of Donald Olding Hebb","volume":"15","author":"Brown R. 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