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Our research with adolescent vs adult male rats, however, shows that rats taking cocaine as adolescents have lower levels of cue\u2010induced reinstatement of drug\u2010seeking than adults, despite similar levels of intravenous (i.v.) cocaine self\u2010administration. Lower rates of reinstatement in younger rats could be explained by higher levels of brain plasticity. Two neuroplasticity\u2010related genes, activity\u2010regulated cytoskeletal\u2010associated gene (<jats:italic>Arc<\/jats:italic>) and brain\u2010derived neurotrophic factor (<jats:italic>Bdnf<\/jats:italic>), influence cocaine self\u2010administration and cue\u2010induced reinstatement. We tested whether reinstatement of cocaine seeking correlates with expression of these genes in reinforcement\u2010related brain regions. Adolescent and adult male rats (postnatal day 35 or 83\u201095 at start) were allowed to acquire lever\u2010pressing maintained by i.v. infusions of cocaine in daily 2\u2010h sessions over 13\u00a0days. At one of three experimental time points, rats were sacrificed and tissue collected to analyze <jats:italic>Arc<\/jats:italic> and <jats:italic>Bdnf<\/jats:italic> mRNA by in situ hybridization in the entire medial prefrontal cortex and entire nucleus accumbens, as well as relevant subregions: prelimbic cortex, infralimbic cortex, and nucleus accumbens core and shell. Despite taking similar amounts of cocaine, adolescents reinstated less than adults. Gene expression was most notable in the prelimbic cortex, was generally higher in adolescent\u2010onset groups, and was higher with longer abstinence. These data partially support the hypothesis that higher levels of <jats:italic>Arc<\/jats:italic> and\/or <jats:italic>Bdnf<\/jats:italic> gene expression in reinforcement\u2010related brain regions of younger animals contribute to lower rates of extinction responding and\/or reinstatement. Future studies should include mechanistic analysis of <jats:italic>Arc<\/jats:italic>, <jats:italic>Bdnf<\/jats:italic>, and their signaling pathways in age\u2010dependent effects of cocaine.<\/jats:p>","DOI":"10.1111\/adb.12689","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T07:17:14Z","timestamp":1542093434000},"page":"1233-1241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<i>ARC<\/i> and <i>BDNF<\/i> expression after cocaine self\u2010administration or cue\u2010induced reinstatement of cocaine seeking in adolescent and adult male rats"],"prefix":"10.1111","volume":"23","author":[{"given":"Chen","family":"Li","sequence":"first","affiliation":[{"name":"Neuroscience Institute Georgia State University  Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandria C.","family":"White","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Georgia State University  Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri","family":"Schochet","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Medical University of South Carolina  Charleston SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-0107","authenticated-orcid":false,"given":"Jacqueline F.","family":"McGinty","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Medical University of South Carolina  Charleston SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9569-468X","authenticated-orcid":false,"given":"Kyle J.","family":"Frantz","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Georgia State University  Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,12]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Monitoring the future: marijuana use is rising; ecstasy use is beginning to rise; and alcohol use is declining among U.S. teens","author":"Johnston LD","year":"2010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsad.2007.68.834"},{"key":"e_1_2_8_4_1","unstructured":"SAMHSA(2017).Center for Behavioral Health Statistics and Quality. 2016 National Suvey on Drug Use and Health: Detailed Tables. 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