Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.
Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana.
Alcohol Clin Exp Res. 2019 Sep;43(9):1937-1948. doi: 10.1111/acer.14150. Epub 2019 Aug 21.
Although not legally allowed to consume alcohol, adolescents account for 11% of all alcohol use in the United States and approximately 90% of adolescent intake is in the form of an alcohol binge. The adolescent intermittent ethanol (AIE) model developed by the NADIA consortium produces binge-like EtOH exposure episodes. The current experiment examined the effects of AIE on the reinforcing properties of EtOH and genetic expression of cholinergic and dopaminergic factors within the posterior ventral tegmental area (pVTA) in Wistar male and female rats and in male alcohol-preferring (P) rats.
Rats were exposed to the AIE or water during adolescence, and all testing occurred during adulthood. Wistar control and AIE rats were randomly assigned to groups that self-administered 0 to 200 mg% EtOH. Male P rats self-administered 0 to 100 mg%.
The data indicated that exposure to AIE in both Wistar male and female rats (and male P rats) resulted in a significant leftward shift in dose-response curve for EtOH self-administration into the pVTA. TaqMan array indicated that AIE exposure had divergent effects on the expression of nicotinic receptors (increased a7, reduction in a4 and a5). There were also sex-specific effects of AIE on gene expression; male only reduction in D3 receptors.
Binge-like EtOH exposure during adolescence enhances the sensitivity to the reinforcing properties of EtOH during adulthood which could be part of biological sequelae that are the basis for the deleterious effects of adolescent alcohol consumption on the rate of alcoholism during adulthood.
尽管在美国，青少年饮酒是违法的，但他们却占了所有饮酒者的 11%，而且大约 90%的青少年摄入的酒精都是暴饮的形式。由 NADIA 联盟开发的青少年间歇性乙醇（AIE）模型会产生类似于狂饮的乙醇暴露发作。目前的实验研究了 AIE 对雄性和雌性 Wistar 大鼠以及雄性酒精偏好（P）大鼠的后腹侧被盖区（pVTA）内的乙醇奖赏属性和胆碱能及多巴胺能因素的基因表达的影响。
青春期时，大鼠暴露于 AIE 或水中，所有测试均在成年期进行。Wistar 对照组和 AIE 组大鼠被随机分配到自行摄入 0 至 200mg%乙醇的组中。雄性 P 大鼠自行摄入 0 至 100mg%乙醇。
数据表明，AIE 暴露会使 Wistar 雄性和雌性大鼠（以及雄性 P 大鼠）的 pVTA 内的乙醇自我给药的剂量-反应曲线发生显著左移。TaqMan 阵列表明，AIE 暴露对烟碱受体的表达有不同的影响（a7 增加，a4 和 a5 减少）。AIE 对基因表达也有性别特异性影响；仅雄性 D3 受体减少。
青春期的狂饮式乙醇暴露会增强成年期乙醇奖赏属性的敏感性，这可能是青少年饮酒对成年期酗酒率的有害影响的生物学后果的一部分。
