Grahame N J, Li T K, Lumeng L
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Alcohol Clin Exp Res. 1999 Jun;23(6):1015-22.
Selection studies and genetic analyses of drinking behavior in rodents often involved unlimited access to alcohol over a period of weeks, with water and food freely available. Most studies investigating the pharmacology of alcohol drinking, on the other hand, use procedures in which access to alcohol is limited to a particular time each day. Reconciliation of findings between these two conditions likely depends on their sharing common genetic mechanisms as indicated, for example, by covariation in response to selection. To this end, high- and low-alcohol preferring (HAP and LAP, respectively) mice, selected for differences in 24-hr access alcohol drinking over a 4-week period, were subjected to a limited access alcohol drinking protocol.
During 2-hr sessions, mice had access to various concentrations of alcohol (7-15%, v/v) in the home cage for 2 hr a day, with ad libitum access to food and water. Additional sessions were conducted with no food present.
Although both strains consumed alcohol and water during these sessions, HAP mice drank far more alcohol than did LAP mice. HAP but not LAP mice drank alcohol at a high rate early in the session compared with later in the session. Additionally, HAP mice responded to changes in alcohol concentration, whereas LAP mice did not. Removal of food did not influence alcohol drinking, although water drinking decreased following food removal. HAP mice reached appreciable blood alcohol concentrations after limited access.
These findings indicate that in these selectively bred mice, alcohol drinking during limited and unlimited access may be genetically related, and that drinking during limited access sessions in HAP mice is likely for the pharmacological properties of alcohol.
啮齿动物饮酒行为的选择研究和基因分析通常涉及数周内无限制地获取酒精,同时可自由获取水和食物。另一方面,大多数研究酒精饮用药理学的实验采用的程序是,每天仅在特定时间允许获取酒精。这两种情况研究结果的一致性可能取决于它们共享的共同遗传机制,例如,通过对选择的反应共变来表明。为此,对在4周内24小时酒精摄入量存在差异的高酒精偏好(分别为HAP)和低酒精偏好(LAP)小鼠进行了有限获取酒精饮用方案的实验。
在2小时的实验时段内,小鼠在笼舍中每天有2小时可获取不同浓度(7 - 15%,v/v)的酒精,同时可随意获取食物和水。还进行了无食物情况下的额外实验时段。
虽然两种品系的小鼠在这些实验时段都摄入了酒精和水,但HAP小鼠比LAP小鼠饮用的酒精要多得多。与实验时段后期相比,HAP小鼠在实验时段早期饮酒速度更快。此外,HAP小鼠对酒精浓度变化有反应,而LAP小鼠则没有。去除食物不影响酒精饮用,不过去除食物后水的饮用减少。有限获取酒精后,HAP小鼠达到了可观的血液酒精浓度。
这些发现表明,在这些选择性培育的小鼠中,有限获取和无限制获取酒精期间的饮酒行为可能存在遗传关联,并且HAP小鼠在有限获取实验时段的饮酒行为可能是出于酒精的药理学特性。