Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University and VA Medical Center, USA.
Alcohol. 2011 Aug;45(5):427-40. doi: 10.1016/j.alcohol.2010.12.001. Epub 2010 Dec 30.
We have selectively bred mice that reach very high blood ethanol concentrations (BECs) after drinking from a single bottle of 20% ethanol. High Drinking in the Dark (HDID-1) mice drink nearly 6g/kg ethanol in 4h and reach average BECs of more than 1.0mg/mL. Previous studies suggest that DID and two-bottle preference for 10% ethanol with continuous access are influenced by many of the same genes. We therefore asked whether HDID-1 mice would differ from the HS/Npt control stock on two-bottle preference drinking. We serially offered mice access to 3-40% ethanol in tap water versus tap water. For ethanol concentrations between 3 and 20%, HDID-1 and HS/Npt controls did not differ in two-bottle preference drinking. At the highest concentrations, the HS/Npt mice drank more than the HDID-1 mice. We also tested the same mice for preference for two concentrations each of quinine, sucrose, and saccharin. Curiously, the mice showed preference ratios (volume of tastant/total fluid drunk) of about 50% for all tastants and concentrations. Thus, neither genotype showed either preference or avoidance for any tastant after high ethanol concentrations. Therefore, we compared naive groups of HDID-1 and HS/Npt mice for tastant preference. Results from this test showed that ethanol-naive mice preferred sweet fluids and avoided quinine but the genotypes did not differ. Finally, we tested HDID-1 and HS mice for an extended period for preference for 15% ethanol versus water during a 2-h access period in the dark. After several weeks, HDID-1 mice consumed significantly more than HS. We conclude that drinking in the dark shows some genetic overlap with other tests of preference drinking, but that the degree of genetic commonality depends on the model used.
我们已经选择性地培育了一些老鼠,这些老鼠在从一瓶 20%的乙醇中喝了酒后,血液中的乙醇浓度(BEC)会非常高。“高暗饮(HDID-1)”老鼠在 4 小时内几乎摄入 6g/kg 的乙醇,并且平均 BEC 超过 1.0mg/ml。以前的研究表明,DID 和用连续通路自由获取的 10%乙醇的双瓶偏好受到许多相同基因的影响。因此,我们想知道 HDID-1 老鼠是否会与 HS/Npt 对照品系在双瓶偏好饮酒方面有所不同。我们连续让老鼠饮用自来水和自来水中的 3-40%乙醇。对于 3-20%的乙醇浓度,HDID-1 和 HS/Npt 对照品系在双瓶偏好饮酒方面没有差异。在最高浓度下,HS/Npt 老鼠的饮酒量超过了 HDID-1 老鼠。我们还测试了相同的老鼠对两种浓度的奎宁、蔗糖和糖精的偏好。奇怪的是,老鼠对所有的味觉剂和浓度都表现出大约 50%的偏好比(味觉剂的体积/饮用的总液体量)。因此,两种基因型在高乙醇浓度后都没有对任何味觉剂表现出偏好或回避。因此,我们比较了 HDID-1 和 HS/Npt 组的老鼠对味觉剂的偏好。这个测试的结果表明,乙醇未接触的老鼠更喜欢甜的液体,回避奎宁,但基因型之间没有差异。最后,我们测试了 HDID-1 和 HS 老鼠在黑暗中对 15%乙醇与水的 2 小时偏好。经过数周,HDID-1 老鼠的摄入量明显高于 HS 老鼠。我们的结论是,暗饮与其他偏好饮酒测试有一定的遗传重叠,但遗传相似性的程度取决于所使用的模型。