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Despite great efforts to understand underlying neurobiological mechanisms of this progression, less attention has been paid to the role of genetic factors. Here, we investigated the influence of both genetic background and age at first nicotine exposure in the long\u2010lasting effects on mesolimbic dopamine transmission including the increased cocaine\u2010rewarding effect. Mid\u2010adolescent and adult rats of inbred strains Lewis (addiction prone) and Fischer 344 (addiction resistant) were administered nicotine (0.4 mg\/kg) or vehicle once daily for 5 days. Changes in dopamine transmission were investigated by in vivo microdialysis and electrophysiology after 30 days of withdrawal, whereas changes in cocaine\u2010rewarding effect were assessed via conditioned place preference paradigm. Nicotine pre\u2010exposure differentially changed mesolimbic dopamine transmission depending on strain and age of pre\u2010exposure. A potentiation of dopamine response to nicotine was observed in nucleus accumbens (NAc) core of both strains and age groups, whereas dopamine response in NAc shell was enhanced exclusively in Lewis rats exposed to nicotine during adolescence. A similar response was observed following cocaine challenge at adulthood. Changes in VTA dopamine cell population and activity were observed only in adolescent nicotine\u2010pretreated Lewis rats, which also showed an increased cocaine\u2010rewarding effect at adulthood. These results highlight the influence of genetic background in the long\u2010lasting effects of nicotine exposure and suggest that exposure during adolescence might increase nicotine and cocaine\u2010rewarding properties in genetically vulnerable individuals, thereby facilitating progression toward dependence.<\/jats:p>","DOI":"10.1111\/adb.12803","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T01:04:15Z","timestamp":1564016655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Role of genetic background in the effects of adolescent nicotine exposure on mesolimbic dopamine transmission"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-4043","authenticated-orcid":false,"given":"Cristina","family":"Cadoni","sequence":"first","affiliation":[{"name":"National Research Council of Italy Institute of Neuroscience  Cagliari 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