Role of genetic background in the effects of adolescent nicotine exposure on mesolimbic dopamine transmission. (24th July 2019)

• Record Type: Journal Article
• Authors: Cadoni, Cristina; De Felice, Marta; Corongiu, Silvia; Dessì, Christian; Espa, Elena; Melis, Miriam; Fenu, Sandro
• Is Part Of: Addiction biology. Volume 25:Number 5(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-07-24
• Subjects: adolescence -- cocaine -- dopamine transmission -- Fischer 344 rats -- Lewis rats -- nicotine -- nucleus accumbens; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12803
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Smoking during adolescence may increase the likelihood to develop nicotine dependence and to abuse other drugs such as cocaine. 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‐lasting effects on mesolimbic dopamine transmission including the increased cocaine‐rewarding effect. Mid‐adolescent 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‐rewarding effect were assessed via conditioned place preference paradigm. Nicotine pre‐exposure differentially changed mesolimbic dopamine transmission depending on strain and age of pre‐exposure. 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‐pretreated Lewis rats, which also showed an increased cocaine‐rewarding effect at adulthood. These results highlight the influence of genetic background in the long‐lasting effects of nicotine exposure and suggest that exposure during adolescence might increase nicotine and cocaine‐rewarding properties in genetically vulnerable individuals, thereby facilitating progression toward dependence. Abstract : Nicotine pre‐exposure differentially affects mesolimbic DA transmission depending on genotype and age of exposure. Here, we show that adolescent nicotine exposure increases DA response to nicotine and cocaine at adulthood in the NAc shell of addiction‐prone Lewis rats. This effect is associated with an increased cocaine‐rewarding effect. Moreover, adolescent nicotine only impacts on the number of spontaneously active VTA DA cells and their firing frequency of Lewis rats.