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Currently, there is no effective treatment or cure for GWI; therefore, there is a critical need to develop experimental models to help better understand its mechanisms and interventions related to GWI\u2010associated neuropsychiatric disorders. Chemical neurotoxicity appears to be one cause of GWI, and its symptoms manifest as disruptions in neuronal function. However, the mechanisms underlying such incapacitating neurologic and psychiatric symptoms are poorly understood. The etiology of GWI is complex, and many factors including chemical exposure, psychological trauma, and environmental stressors have been associated with its development. Attempts have been made to create GWI\u2010like symptomatic models, including through chronic induction in mice and rats. Here, we present a brief protocol of GWI in rats and mice, which exhibit robust neuropsychiatric signs and neuropathologic changes reminiscent of GWI. This article provides a guide to working protocols, application of therapeutic drugs, outcomes, troubleshooting, and data analysis. Our broad profiling of GWI\u2010like symptoms in rodents reveals features of progressive morphologic and long\u2010lasting neuropsychiatric features. Together, the GWI model in rodents shows striking consistency in recapitulating major hallmark features of GWI in veterans. These models help identify mechanisms and interventions for GWI. \u00a9 2023 Wiley Periodicals LLC.<\/jats:p><jats:p><jats:bold>Basic Protocol 1<\/jats:bold>: Experimental induction of Gulf War illness in rats<\/jats:p><jats:p><jats:bold>Support Protocol 1<\/jats:bold>: Monitoring of Gulf War illness signs and neuroimaging analysis in rats<\/jats:p><jats:p><jats:bold>Basic Protocol 2<\/jats:bold>: Experimental induction of Gulf War illness in mice<\/jats:p><jats:p><jats:bold>Support Protocol 2<\/jats:bold>: Monitoring of Gulf War illness signs and neuropathology analysis in mice<\/jats:p>","DOI":"10.1002\/cpz1.707","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T18:54:21Z","timestamp":1679511261000},"source":"Crossref","is-referenced-by-count":7,"title":["Experimental Models of Gulf War Illness, a Chronic Neuropsychiatric Disorder in Veterans"],"prefix":"10.1002","volume":"3","author":[{"given":"Doodipala Samba","family":"Reddy","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"},{"name":"Institute of Pharmacology and Neurotherapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"},{"name":"School of Engineering Medicine (EnMed) Texas A&amp;M University  Houston Texas"},{"name":"Department of Biomedical Engineering, College of Engineering Texas A&amp;M University  College Station Texas"},{"name":"Department of Veterinary Integrative Biosciences, College of Veterinary Medicine &amp; Biomedical Sciences Texas A&amp;M University  College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"},{"name":"Institute of Pharmacology and Neurotherapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanveer","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"},{"name":"Institute of Pharmacology and Neurotherapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Neff","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"},{"name":"Institute of Pharmacology and Neurotherapeutics, School of Medicine Texas A&amp;M University Health Science Center  Bryan Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017\u2010011\u20108160\u2010z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017\u2010012\u20108192\u2010z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2013.10.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2016.10.012"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2003.10.018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/009841096161456"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172914"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.07.015"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1099\u20101263(199707)17"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2021.107012"},{"issue":"4","key":"e_1_2_9_12_1","first-page":"214","article-title":"Potentiation of pyridostigmine bromide toxicity in mice by selected adrenergic agents and caffeine","volume":"39","author":"Chaney L. 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