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However, it can be difficult to ascertain from clinical data whether the <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> is cause or consequence of increased addiction vulnerability. Surprisingly few studies have taken advantage of animal models to investigate the causal nature of this relationship. In terms of a plausible neurobiological mechanism through which <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> could magnify the risk of substance dependence, numerous studies indicate that <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> can cause widespread disruption to monoaminergic signaling in striatal regions, and also increases neuroinflammation. In the current study, male Long\u2010Evans rats received either a mild or severe <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> centered over the frontal cortex via controlled cortical impact, and were subsequently trained to self\u2010administer cocaine over 10 6\u2010hour sessions. At the end of the study, markers of striatal dopaminergic function, and levels of inflammatory cytokine levels in the frontal lobes, were assessed via western blot and multiplex <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>, respectively. There was significantly higher cocaine intake in a subset of animals with either mild or severe <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content>. However, many animals within both <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> groups failed to acquire self\u2010administration. Principal components analysis suggested that both dopaminergic and neuroinflammatory proteins were associated with overall cocaine intake, yet only an inflammatory component was associated with acquisition of self\u2010administration, suggesting neuroinflammation may make a more substantial contribution to the likelihood of drug\u2010taking. Should neuroinflammation play a causal role in mediating <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content>\u2010induced addiction risk, anti\u2010inflammatory therapy may reduce the likelihood of substance abuse in <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> populations.<\/jats:p>","DOI":"10.1111\/ejn.14123","type":"journal-article","created":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T20:24:43Z","timestamp":1534537483000},"page":"2134-2145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Cocaine self\u2010administration is increased after frontal traumatic brain injury and associated with neuroinflammation"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-2068","authenticated-orcid":false,"given":"Cole","family":"Vonder Haar","sequence":"first","affiliation":[{"name":"Injury and Recovery Laboratory Department of Psychology West Virginia University PO Box\u00a06040 53 Campus Drive Morgantown WV 26505 USA"},{"name":"Laboratory of Molecular and Behavioural Neuroscience University of British Columbia 2215 Wesbrook Mall Vancouver BC V6T 1Z3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline\u2010Marie N.","family":"Ferland","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Behavioural Neuroscience University of British Columbia 2215 Wesbrook Mall Vancouver BC V6T 1Z3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhbir","family":"Kaur","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Behavioural Neuroscience University of British Columbia 2215 Wesbrook Mall Vancouver BC V6T 1Z3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara\u2010Kirstie","family":"Riparip","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Center Departments of Physical Therapy Rehabilitation Science and Neurological Surgery University of California San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Rosi","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Center Departments of Physical Therapy Rehabilitation Science and Neurological Surgery University of California San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine A.","family":"Winstanley","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Behavioural Neuroscience University of British Columbia 2215 Wesbrook Mall Vancouver BC V6T 1Z3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-015-9792-y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.0135"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00049"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.03.011"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001199-200509000-00006"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.019"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158136"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02294361"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.08.012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.534807"},{"key":"e_1_2_10_12_1","unstructured":"Center for Behavioral Health Statistics and Quality(2015)Behavioral health trends in the United States: Results from the 2014 Survey on Drug Use and Health. 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