Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, and VA Medical Center, Portland, OR 97239, USA.
Alcohol Clin Exp Res. 2012 Jul;36(7):1162-70. doi: 10.1111/j.1530-0277.2012.01735.x. Epub 2012 Feb 8.
Mouse lines are being selectively bred in replicate for high blood ethanol concentrations (BECs) achieved after a short period of ethanol (EtOH) drinking early in the circadian dark phase. High Drinking in the Dark-1 (HDID-1) mice were in selected generation S18, and the replicate HDID-2 line in generation S11.
To determine other traits genetically correlated with high DID, we compared naïve animals from both lines with the unselected, segregating progenitor stock, HS/Npt. Differences between HDID-1 and HS would imply commonality of genetic influences on DID and these traits.
HDID-1 mice showed less basal activity, greater EtOH stimulated activity, and greater sensitivity to EtOH-induced foot slips than HS. They showed lesser sensitivity to acute EtOH hypothermia and longer duration loss of righting reflex than HS. HDID-1 and control HS lines did not differ in sensitivity on 2 measures of intoxication, the balance beam and the accelerating rotarod. None of the acute response results could be explained by differences in EtOH metabolism. HDID-2 differed from HS on some, but not all, of the above responses.
These results show that some EtOH responses share common genetic control with reaching high BECs after DID, a finding consistent with other data regarding genetic contributions to EtOH responses.
正在通过选择性繁殖来培育一批对在昼夜节律的暗期早期饮用少量乙醇(EtOH)后达到的高血液乙醇浓度(BEC)有反应的小鼠品系。高饮酒黑暗 1 型(HDID-1)小鼠处于选择的第 S18 代,而重复的 HDID-2 系处于第 S11 代。
为了确定与高 DID 遗传相关的其他特征,我们比较了来自两个系的未接触过的原始动物与未选择的、分离的祖先品系 HS/Npt。HDID-1 与 HS 之间的差异意味着 DID 和这些特征的遗传影响具有共同性。
HDID-1 小鼠的基础活动较少,乙醇刺激的活动较多,对乙醇引起的足滑的敏感性较大,比 HS 更大。它们对急性乙醇低温的敏感性较低,对翻正反射的持续时间损失较长,比 HS 更长。HDID-1 和对照 HS 系在 2 种中毒测量指标(平衡木和加速转棒)上的敏感性没有差异。急性反应结果都不能用乙醇代谢的差异来解释。HDID-2 与 HS 在上述一些但不是所有反应上存在差异。
这些结果表明,一些乙醇反应与 DID 后达到高 BEC 具有共同的遗传控制,这与其他关于乙醇反应遗传贡献的数据一致。