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Here, we show how exposure to sucrose, which is ubiquitously available in modern diets, results in changes in behavioural response to cocaine as an adult. Rats were given daily access to either 10% sucrose or water during the adolescent period (PND28\u201342). Following this period, rats are left undisturbed until they reach adulthood. In adulthood, rats were tested for (i) acquisition of a low dose of cocaine, (ii) progressive ratio (PR) test, and (iii) resistance to punished cocaine taking. Sucrose exposure resulted in significant alterations in all behavioural measures. To determine the neurobiological mechanisms leading to such behavioural adaptations, we find that adolescent sucrose exposure results in an upregulation of the transcription factor Smad3 in the nucleus accumbens (NAc) when compared with water\u2010exposed controls. Transiently blocking the active form of this transcription factor (HSV\u2010dnSmad3) during adolescence mitigated the enhanced cocaine vulnerability\u2010like behaviours observed in adulthood. These findings suggest that prior exposure to sucrose during adolescence can heighten the reinforcing effects of cocaine. Furthermore, they identify the TGF\u2010beta pathway and Smad3 as playing a key role in mediating enduring and long\u2010lasting adaptations that contribute to sucrose\u2010induced susceptibility to cocaine. Taken together, these results have important implications for development and suggest that adolescent sucrose exposure may persistently enhance the susceptibility to substance abuse.<\/jats:p>","DOI":"10.1111\/adb.13346","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T16:13:44Z","timestamp":1698423224000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adolescent exposure to sucrose increases cocaine\u2010mediated behaviours in adulthood via Smad3"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-9732","authenticated-orcid":false,"given":"Amy M.","family":"Gancarz","sequence":"first","affiliation":[{"name":"Department of Psychology California State University  Bakersfield California USA"},{"name":"Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"},{"name":"Clinical and Research Institute on Addictions University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raveena","family":"Parmar","sequence":"additional","affiliation":[{"name":"Department of Psychology California State University  Bakersfield California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Treefa","family":"Shwani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moriah M.","family":"Cobb","sequence":"additional","affiliation":[{"name":"Department of Psychology California State University  Bakersfield California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle N.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Psychology California State University  Bakersfield California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob R.","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Psychology California State University  Bakersfield California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Psychology California State University  Bakersfield California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Kausch","sequence":"additional","affiliation":[{"name":"Department of Psychology California State University  Bakersfield California USA"},{"name":"Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig T.","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-9236","authenticated-orcid":false,"given":"David M.","family":"Dietz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York USA"},{"name":"Clinical and Research Institute on Addictions University at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Publication No. PEP22\u201007\u201001\u2010005 NSDUH Series H\u201057. 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