Grahame N J, Rodd-Henricks K, Li T K, Lumeng L
Department of Medicine, Institute for Psychiatric Research, Indianapolis, IN 46202, USA.
Psychopharmacology (Berl). 2000 Aug;151(2-3):252-60. doi: 10.1007/s002130000388.
Some theories have advanced a role for both locomotor sensitization and tolerance in the reinforcing properties of drugs. The present studies used selected lines of mice to assess genetic correlations among ethanol drinking, ethanol locomotor sensitization, and tolerance to the depressant effects of ethanol.
Ethanol-naive high- and low-alcohol preferring (HAP and LAP) selected lines of mice were tested for locomotor sensitization to ethanol and acquisition of acute functional tolerance to ethanol using the static dowel test.
For the locomotor sensitization study, mice received four i.p. injections of one of five doses of ethanol (0-3.5 g/kg) at 48-h intervals. On the sensitization test day, 48 h after the last drug administration day, all mice received a 2.0-g/kg ethanol injection. Other mice from the same lines were subjected to a two-injection (3.75 g/kg total), acute functional tolerance procedure assessing disruption of balance on a static dowel.
Lines differed neither in the acute locomotor activating nor depressant effects of ethanol. Additionally, neither line's response to the depressant effect of 3.5 g/kg ethanol changed with repeated injection. However, locomotor sensitization was seen in HAP but not LAP mice that had received 2.75 g/kg or 3.5 g/kg ethanol during repeated administration. Both HAP and LAP mice acquired equivalent acute functional tolerance, as measured by an increase in blood ethanol concentration between the first and second recovery measures.
Overall, these findings imply that high ethanol consumption in mice appears to be genetically related to ethanol locomotor sensitization. Additionally, ethanol locomotor sensitization does not appear to be related to tolerance to the depressant effects of ethanol. These findings support a role for sensitization in high alcohol-seeking behavior in mice.
一些理论提出运动致敏和耐受在药物强化特性中都起作用。本研究使用特定品系的小鼠来评估乙醇摄入、乙醇运动致敏和对乙醇抑制作用的耐受之间的遗传相关性。
对未接触过乙醇的高酒精偏好（HAP）和低酒精偏好（LAP）小鼠品系进行测试，以使用静态木钉试验评估其对乙醇的运动致敏以及对乙醇急性功能耐受的获得情况。
在运动致敏研究中，小鼠每隔48小时腹腔注射五种剂量（0 - 3.5克/千克）乙醇中的一种，共注射四次。在致敏测试日，即最后一次给药日后48小时，所有小鼠接受2.0克/千克乙醇注射。来自同品系的其他小鼠接受两次注射（总计3.75克/千克）的急性功能耐受程序，评估在静态木钉上平衡的破坏情况。
各品系在乙醇的急性运动激活或抑制作用方面均无差异。此外，重复注射后，两品系对3.5克/千克乙醇抑制作用的反应均未改变。然而，在重复给药期间接受2.75克/千克或3.5克/千克乙醇的HAP小鼠中观察到运动致敏，而LAP小鼠未观察到。通过第一次和第二次恢复测量之间血液乙醇浓度的增加来衡量，HAP和LAP小鼠获得了同等程度的急性功能耐受。
总体而言，这些发现表明小鼠的高乙醇摄入量似乎与乙醇运动致敏存在遗传关联。此外，乙醇运动致敏似乎与对乙醇抑制作用的耐受无关。这些发现支持致敏在小鼠高酒精寻求行为中的作用。
