Department of Pharmaceutical Sciences , University of Colorado Anschutz Medical Campus, Aurora, Colorado; Institute for Behavioral Genetics , University of Colorado, Boulder, Colorado.
Alcohol Clin Exp Res. 2013 Dec;37(12):2019-28. doi: 10.1111/acer.12188. Epub 2013 Jul 24.
We hypothesized that rapid tolerance (1-day tolerance) for the duration of the loss of righting reflex ("sleep time" [ST]) was mediated by an increase in acute functional tolerance (AFT). We also hypothesized that increased AFT would correspond to increased drinking. These questions were addressed using the LXS recombinant inbred mouse strain panel.
Mice were given a pretreatment dose of either saline or 5 g/kg alcohol on day 1. On day 2, mice were tested for ST (4.1 g/kg) using a method with which it is possible to accurately assess AFT. Genetic correlation analysis was conducted among the ST-related variables and also with "drinking in the dark" (DID) which was previously measured by Saba and colleagues (2011).
Saline-pretreated mice showed a continuous distribution of ST ranging from ~40 minutes to over 3 hours. Of the 43 strains tested, 9 showed significantly decreased ST after alcohol pretreatment, while in 3 strains, ST was significantly increased. AFT scores ranged from 0 to over 200 mg% in the saline group, and in the alcohol group, 8 strains showed a significant increase in AFT and 2 strains showed significant decrease in AFT. In the saline group, AFT was significantly correlated with ST (r = -0.47), but not in the alcohol group (r = -0.22). DID was significantly correlated with only AFT in the alcohol pretreated group (r = 0.64).
The results suggest that AFT is an important component of the overall ST response, but that the alcohol pretreatment-induced change in AFT does not contribute to rapid ST tolerance. The significant correlation between DID and AFT in the alcohol group suggests that AFT may be a more relevant predictor of drinking behavior than the static measurement of ST. Moreover, preexposure to alcohol seems to change AFT in a way that makes it an even stronger predictor of drinking behavior.
我们假设快速耐受（失去翻正反射的持续时间[ST] 1 天的耐受）是由急性功能耐受（AFT）增加介导的。我们还假设，增加 AFT 将对应于增加饮酒量。使用 LXS 重组近交系小鼠品系小组来解决这些问题。
第一天，给小鼠给予生理盐水或 5 g/kg 酒精的预处理剂量。在第二天，使用一种可以准确评估 AFT 的方法对 ST（4.1 g/kg）进行测试。对与 ST 相关的变量以及 Saba 和同事（2011 年）之前测量的“暗饮”（DID）之间进行遗传相关性分析。
生理盐水预处理的小鼠的 ST 呈连续分布，范围从 ~40 分钟到 3 小时以上。在测试的 43 个品系中，有 9 个在酒精预处理后 ST 明显降低，而在 3 个品系中，ST 明显增加。AFT 评分在生理盐水组的范围从 0 到超过 200mg%，而在酒精组中，8 个品系的 AFT 显著增加，2 个品系的 AFT 显著降低。在生理盐水组中，AFT 与 ST 显著相关（r=-0.47），但在酒精组中不相关（r=-0.22）。DID 仅与酒精预处理组的 AFT 显著相关（r=0.64）。
结果表明，AFT 是总体 ST 反应的重要组成部分，但酒精预处理诱导的 AFT 变化不会导致快速 ST 耐受。酒精组中 DID 与 AFT 之间的显著相关性表明，AFT 可能是饮酒行为的更相关预测因子，而不是 ST 的静态测量。此外，酒精的预暴露似乎以一种使 AFT 成为更强大的饮酒行为预测因子的方式改变 AFT。
