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Thus, the aim of this study is to test the hypothesis that at an age of ongoing maturation, adolescent TBI alters elements of the reward pathway, resulting in increased sensitivity to the rewarding effects of a subthreshold dose of cocaine that does not induce significant behavioral changes in na\u00efve, non-injured mice. Specifically, these results were derived from the combination of the controlled cortical impact model of TBI, performed on either adolescent (6 weeks) or young adult (8 weeks) mice, followed by the cocaine-induced conditioned place preference assay 2 weeks later. Using three-dimensional isosurface rendering and volumetric image analysis, TBI was found to induce neuromorphological changes such as decreased dendritic complexity and reduced spine density in brain regions essential for reward perception and processing of drug-induced euphoria. Further, we demonstrated that these neuronal changes may affect the differential expression of dopamine-associated genes. Our analysis also provided evidence for age-related differences in immune response and the distinct involvement of augmented microglial phagocytic activity in the remodeling of neuronal structures in the adolescent TBI brain. Our studies suggest that TBI during adolescence, a period associated with ongoing maturation of dopaminergic systems, may subsequently enhance the abuse liability of cocaine in adulthood.<\/jats:p>","DOI":"10.1089\/neu.2019.6472","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T07:38:48Z","timestamp":1564126728000},"page":"27-42","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Experimental Traumatic Brain Injury during Adolescence Enhances Cocaine Rewarding Efficacy and Dysregulates Dopamine and Neuroimmune Systems in Brain Reward Substrates"],"prefix":"10.1177","volume":"37","author":[{"given":"Lee Anne","family":"Cannella","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison M.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fionya","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshanak","family":"Razmpour","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"McGary","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ceryce","family":"Collie","sequence":"additional","affiliation":[{"name":"Department of Biology, Lincoln University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarik","family":"Tsegaye","sequence":"additional","affiliation":[{"name":"Department of Biology, Lincoln University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marquis","family":"Maynard","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc J.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Rawls","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Servio H.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University, Philadelphia Pennsylvania."},{"name":"Center for Substance Abuse Research, Temple University, Philadelphia Pennsylvania."},{"name":"Shriners Hospital for Pediatric Research Center, Temple University, Philadelphia Pennsylvania."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.15620\/cdc.5571"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss6609a1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001199-200609000-00001"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11126-018-9617-0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/HTR.0b013e3181a712aa"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2011.648705"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/02699050801938967"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617708080272"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/HTR.0000000000000156"},{"key":"e_1_3_4_11_2","unstructured":"Substance Abuse and Mental Health Services Administration. 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