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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Sensitivity and tolerance to ethanol in mouse lines selected for ethanol-induced hypothermia.
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Sensitivity and tolerance to ethanol in mouse lines selected for ethanol-induced hypothermia.

机译：乙醇诱导的体温过低的小鼠品系中对乙醇的敏感性和耐受性。

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Within-family selective breeding techniques have been used to create two lines of mice to be insensitive (HOT) and two lines to be sensitive (COLD) to the hypothermic effects of an acute 3.0-g/kg ethanol (EtOH) injection. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. The breeding program is currently in selected Generation 52, and the HOT and COLD mice differ by about 10 degrees C (average of both replicates) in their selected hypothermic response. Starting with selection Generation 20, separate lines of mice were inbred from the HOT-2 and COLD-2 selected lines, while selection continued for the original two replicate lines of HOT and COLD mice. To assess whether different dose treatments would produce differential tolerance development in the HOT and COLD selected lines, we administered different dose regimens across 5 days to HOT and COLD mice. The COLD mice developed tolerance while the HOT mice did not, regardless of total EtOH administered. In a separate study, we administered EtOH (3.0 g/kg) to mice for 3 days to assess a shorter tolerance paradigm. We also present here responses to the selection dose of 3.0-g/kg EtOH in the inbred HOT (IHOT-2) and COLD (ICOLD-2) mice tested after 41 generations of brother-sister mating. In addition, we report recent attempts to find doses of EtOH that would produce an equivalent initial hypothermic response in each of the six lines (HOT-1, COLD-1, HOT-2, COLD-2, ICOLD-2, and IHOT-2). When doses were selected to produce similar initial hypothermic sensitivity, tolerance was tested by giving three daily doses and examining the attenuation of the hypothermic response on the third day. All three COLD lines developed significant tolerance, while the HOT lines did not. The HOT and COLD mice provide a genetic model to study mechanisms mediating acute EtOH-induced hypothermia as well as tolerance development.
机译：家庭内选择性育种技术已用于创建两行对急性3.0 g / kg乙醇（EtOH）注射的低温效应不敏感（HOT）的小鼠和两对敏感（COLD）的小鼠。先前的研究发现，HOT小鼠对这种效应的耐受性产生相对抵抗，而COLD小鼠则容易产生耐受性。该育种程序目前在选定的第52代中进行，HOT和COLD小鼠在选定的低温反应中相差约10摄氏度（两个重复实验的平均值）。从第20代选择开始，从HOT-2和COLD-2选择的系中分离出单独的小鼠系，同时继续对HOT和COLD小鼠的原始两个复制系进行选择。为了评估不同剂量的治疗是否会在HOT和COLD所选品系中产生不同的耐受性，我们在5天之内对HOT和COLD小鼠施用了不同的剂量方案。不管施用的总EtOH量如何，COLD小鼠都能耐受，而HOT小鼠则不能。在另一项研究中，我们将EtOH（3.0 g / kg）给予小鼠3天，以评估较短的耐受性范式。我们还在此处介绍了41代兄弟姐妹交配后测试的近交HOT（IHOT-2）和COLD（ICOLD-2）小鼠对3.0-g / kg EtOH选择剂量的反应。此外，我们报告了最近的尝试，以寻找在六种系（HOT-1，COLD-1，HOT-2，COLD-2，ICOLD-2和IHOT- 2）。当选择产生相似的初始低温敏感性的剂量时，通过给予三个每日剂量并在第三天检查低温反应的减弱来测试耐受性。所有三条冷线都具有显着的耐受性，而热线则没有。 HOT和COLD小鼠提供了一种遗传模型，用于研究介导急性EtOH诱导的体温过低以及耐受性发展的机制。

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