Crabbe John C, Metten Pamela, Ponomarev Igor, Prescott Carol A, Wahlsten Douglas
Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, 97239, USA.
Behav Genet. 2006 Jul;36(4):536-52. doi: 10.1007/s10519-006-9067-6. Epub 2006 Apr 18.
Mice from eight inbred strains were studied for their acute sensitivity to ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction from pre-injection baseline of their body temperature. Two weeks later, mice were tested for their loss of righting reflex (LRR) after a higher dose of ethanol. The LRR was tested using the "classical" method of watching for recovery in animals placed on their backs in a V-shaped trough and recording duration of LRR. In a separate test, naive animals of the same strains were tested for HT repeatedly to assess the development of rapid (RTOL) and chronic tolerance (CTOL). We have recently developed a new method for testing LRR that leads to a substantial increase in the sensitivity of the test. Strains also have been found to differ in the new LRR test, as well as in the development of acute functional tolerance (AFT) to this response. In addition, our laboratory has periodically published strain difference data on the older versions of the HT and LRR responses. The earlier tests used some of the exact substrains tested currently, while for some strains, different substrains (usually, Nih versus Jax) were tested. We examined correlations of strain means to see whether patterns of strain differences were stable across time and across different test variants assessing the same behavioral construct. HT strain sensitivity scores were generally highly correlated across a 10-23 years period and test variants. The CTOL to HT was well-correlated across studies, and was also genetically similar to RTOL. The AFT, however, was related to neither RTOL nor CTOL, although this may be because different phenotypic end points were compared. The LRR data, which included a variant of the classical test, were not as stable. Measures of LRR onset were reasonably well correlated, as were those taken at recovery (e.g., duration). However, the two types of measures of LRR sensitivity to ethanol appear to be tapping traits that differ genetically. Also, the pattern of genetic correlation between HT and LRR initially reported in 1983 was not seen in current and contemporaneous studies. In certain instances, substrain seems to matter little, while in others, substrains differed a great deal. These data are generally encouraging about the stability of genetic differences.
研究了八个近交系小鼠对乙醇的急性敏感性，以体温降低程度（HT）为指标，体温降低程度以注射前体温基线的下降幅度来衡量。两周后，对小鼠进行更高剂量乙醇处理后的翻正反射丧失（LRR）测试。LRR采用“经典”方法进行测试，即观察置于V形槽中背部着地的动物恢复情况，并记录LRR持续时间。在另一项测试中，对相同品系的未处理动物反复进行HT测试，以评估快速耐受（RTOL）和慢性耐受（CTOL）的发展情况。我们最近开发了一种新的LRR测试方法，该方法可显著提高测试的敏感性。研究发现，各品系在新的LRR测试以及对该反应的急性功能耐受（AFT）发展方面也存在差异。此外，我们实验室定期公布关于HT和LRR反应旧版本的品系差异数据。早期测试使用了一些目前测试的相同亚系，而对于某些品系，则测试了不同的亚系（通常是日本国立卫生研究院品系与杰克逊实验室品系）。我们检查了品系均值的相关性，以确定品系差异模式在时间上以及在评估相同行为结构的不同测试变体中是否稳定。HT品系敏感性评分在10至23年期间和不同测试变体中通常高度相关。不同研究中对HT的CTOL相关性良好，并且在基因上也与RTOL相似。然而，AFT与RTOL和CTOL均无关，尽管这可能是因为比较了不同的表型终点。包括经典测试变体的LRR数据不太稳定。LRR开始时间的测量相关性较好，恢复时的测量（如持续时间）也是如此。然而，两种LRR对乙醇敏感性的测量似乎反映了基因上不同的特征。此外，1983年最初报道的HT和LRR之间的遗传相关性模式在当前和同期研究中未观察到。在某些情况下，亚系似乎影响不大，而在其他情况下，亚系差异很大。这些数据总体上表明遗传差异具有稳定性，令人鼓舞。
