Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA.
Alcohol Clin Exp Res. 2011 Oct;35(10):1842-51. doi: 10.1111/j.1530-0277.2011.01528.x. Epub 2011 May 16.
Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA).
Binge-like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl).
Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice.
These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge-like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol.
青少年时期狂饮酒精是一个严重的健康问题，可能会增加日后患上酒精使用障碍的风险。虽然有几种不同的程序可以在临床前模拟类似狂欢的酒精摄入，但有限访问程序具有实现高自愿性酒精摄入和药理学相关血液酒精浓度（BAC）的优势。因此，在当前的研究中，使用有限访问循环程序检查了类似狂欢的酒精摄入的发育差异。此外，由于酒精摄入与对酒精的厌恶特性的敏感性呈负相关，因此我们检查了对酒精引起的条件味觉厌恶（CTA）的敏感性的发育差异。
在 16 天的时间里，每天 2 到 4 小时，对 4 周龄（青少年）和 10 周龄（成年）雄性 C57BL/6J 小鼠进行类似狂欢的酒精消费。在青少年和成年小鼠中，用盐水或酒精（3 或 4 g/kg）重复与摄入新味觉剂（NaCl）配对，检查对酒精引起的 CTA 的敏感性的发育差异。
与成年小鼠相比，青少年小鼠的酒精摄入量明显增加，青少年小鼠达到更高的 BAC 并在狂欢程序的连续循环中增加酒精摄入量。相反，与成年小鼠相比，青少年小鼠对酒精的厌恶特性的敏感性呈剂量依赖性降低，而青少年小鼠对 3 g/kg 酒精没有产生 CTA。最后，在青少年小鼠中用更高剂量的酒精进行条件作用后观察到酒精 CTA 的消退。
这些结果表明，与成年小鼠相比，在类似狂欢的酒精摄入模型中，青少年小鼠每公斤体重消耗更多的酒精，并且对酒精的条件厌恶作用的敏感性降低。总体而言，这支持了一种行为框架，即青少年时期的狂欢性酒精摄入增加，部分原因是对酒精的厌恶特性的敏感性降低。
