Portland Alcohol Research Center, Research Service, VA Medical Center, OR 97239, USA.
Pharmacol Biochem Behav. 2011 Apr;98(2):279-85. doi: 10.1016/j.pbb.2011.01.003. Epub 2011 Jan 14.
Adult risk of alcohol dependence increases the younger one first engages in intoxicating consumption. Adolescent mice drink more ethanol than do adults on a gram per kilogram basis, an increase sometimes persisting into adulthood, and this is genotype-dependent. Most studies have used 24 h two-bottle preference, with a choice between ethanol and water. We studied the developmental onset of binge drinking using limited access ethanol drinking in the dark (DID) in male and female mice. To establish age dependence in DID magnitude, we tested HS/Npt mice of 6 ages for DID for 2 weeks, and when they were 9 weeks old, we retested them for 2 weeks vs naïve adult controls. Age groups drank equivalently in their first week; thus, adolescent HS/Npt mice do not show greater DID than adults. Six week old mice drank more ethanol during their second week relative to their other weeks. Ethanol DID during early adolescence (4 weeks) led to increased drinking in adulthood, as did initial DID exposure at 8 weeks. High drinking in the dark-1 (HDID-1) mice (4, 6, 9 weeks old), selectively bred for high blood ethanol after DID, were tested for 9 weeks. Mice beginning at 4 weeks generally drank more ethanol than those of other age groups. Comparison at the same ages showed that 9 week olds initiated at 4 weeks drank more ethanol than did naïve 9 week olds, but all three groups of age-matched mice drank equivalent amounts once they were 10 weeks and older. The DID test is thus sensitive to developmental age. DID intakes by young adolescent HDID-1 mice were greater than intakes by older mice, like those shown by studies with two-bottle preference. Early DID led to increased drinking as adults only in HS/Npt mice. HDID-1 mice provide a useful animal model for exploring whether DID and continuous access preference drinking have parallel consequences when initiated in adolescence.
成年人开始饮酒的年龄越小,日后出现酒精依赖的风险就越高。与成年老鼠相比,未成年老鼠在摄入每公斤体重的乙醇量上更多,而且这种情况有时会持续到成年,这种现象依赖于老鼠的基因型。大多数研究都使用了 24 小时双瓶选择实验,即在乙醇和水之间进行选择。我们使用限时黑暗摄入乙醇(DID)方法在雄性和雌性老鼠身上研究了 binge drinking 的发展起始。为了在 DID 量上建立年龄依赖性,我们对 6 个年龄的 HS/Npt 老鼠进行了 2 周的 DID 测试,当它们 9 周大时,我们用它们与未经处理的成年对照组进行了 2 周的对比测试。在第一周,各个年龄组的老鼠饮酒量相当;因此,青春期的 HS/Npt 老鼠并没有比成年老鼠表现出更大的 DID。与其他周相比,6 周大的老鼠在第二周内摄入了更多的乙醇。青少年早期(4 周)的 DID 导致成年期饮酒量增加,而 8 周时初次 DID 暴露也会导致这种情况。DID 后血液中乙醇含量较高的高饮酒量暗 1 型(HDID-1)老鼠(4、6、9 周大),被用于进行 9 周的测试。一般来说,从 4 周大开始的老鼠比其他年龄组的老鼠摄入更多的乙醇。在相同年龄的比较中,从 4 周大开始的 9 周大老鼠摄入的乙醇比未经处理的 9 周大老鼠多,但所有三组年龄匹配的老鼠一旦到了 10 周及以上,摄入的乙醇量就相同了。因此,DID 测试对发育期年龄很敏感。年轻的 HDID-1 老鼠的 DID 摄入量比年长老鼠高,与使用双瓶偏好的研究结果相似。只有在 HS/Npt 老鼠中,早期的 DID 才会导致成年后饮酒量增加。HDID-1 老鼠为探索青春期开始时 DID 和连续摄入偏好饮酒是否具有平行后果提供了一个有用的动物模型。