Tampier L, Quintanilla M E, Mardones J
Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, School of Medicine, University of Chile, Santiago.
J Stud Alcohol. 2000 Sep;61(5):647-51. doi: 10.15288/jsa.2000.61.647.
Studies in mice and rats bred for their behavioral response to ethanol have revealed that there may be a relationship between acute tolerance development, sensitivity to ethanol and alcohol preference. We saw a need to obtain more genetically meaningful correlations between ethanol consumption and acute tolerance to motor impairment or sensitivity to hypothermia induced by ethanol. In the present article, we provide results on acute tolerance, sensitivity to hypothermia and voluntary ethanol consumption in an F2 generation of a cross between inbred UChA (low) and UChB (high) ethanol-consuming rats.
Naive UChA and UChB rats were tested for acute tolerance development to motor impairment and sensitivity to hypothermia induced by the intraperitoneal administration of a dose of ethanol of 2.3 g/kg body weight. Rats were then offered ad libitum a 10% v/v ethanol solution, distilled water and rat food, and classified according to their drinking scores. Next, one female UChA (low consumer) was mated with one male UChB (high consumer) and one female UChB (high consumer) mated with one male UChA (low consumer). The F2 generation of these inbred rats was used to test acute tolerance, sensitivity and voluntary ethanol consumption.
UChB rats developed acute tolerance more rapidly and were less sensitive to the ethanol dose than UChA rats. The F2 generation was designated Hybrid A (HA) for those offspring from the UChA female grandparent and Hybrid B (HB) for the offspring from the UChB female. Results show clearly that there is a relationship between the ability of the rat to acquire acute tolerance to motor impairment, the sensitivity to hypothermia induced by ethanol, and the ethanol preference of the rat. The multiple correlation analysis between the three behaviors showed a significant value in HA rats (r = -0.76, p < .01) and in HB rats (r = -0.83, p < .01).
This study of a cross between UChA and UChB rats showed that the three parameters are related since they clustered together in the F2 generation. This result leads us to speculate that if we could control acute tolerance development in the rats we might also control their voluntary ethanol consumption.
对因对乙醇的行为反应而培育的小鼠和大鼠的研究表明，急性耐受性发展、对乙醇的敏感性和酒精偏好之间可能存在关联。我们认为有必要在乙醇摄入量与对运动障碍的急性耐受性或对乙醇诱导的体温过低的敏感性之间获得更具遗传学意义的相关性。在本文中，我们提供了近交系低乙醇消耗的UChA大鼠和高乙醇消耗的UChB大鼠杂交F2代的急性耐受性、对体温过低的敏感性和自愿乙醇摄入量的结果。
对未经处理的UChA和UChB大鼠进行测试，以观察其对腹腔注射2.3 g/kg体重乙醇所致运动障碍的急性耐受性发展情况以及对体温过低的敏感性。然后随意给大鼠提供10%（v/v）乙醇溶液、蒸馏水和大鼠食物，并根据它们的饮酒评分进行分类。接下来，将一只雌性UChA（低饮酒量者）与一只雄性UChB（高饮酒量者）交配，一只雌性UChB（高饮酒量者）与一只雄性UChA（低饮酒量者）交配。这些近交系大鼠的F2代用于测试急性耐受性、敏感性和自愿乙醇摄入量。
与UChA大鼠相比，UChB大鼠急性耐受性发展更快，对乙醇剂量的敏感性更低。F2代中，来自UChA雌性祖代的后代被指定为杂交A（HA），来自UChB雌性的后代被指定为杂交B（HB）。结果清楚地表明，大鼠获得对运动障碍的急性耐受性的能力、对乙醇诱导的体温过低的敏感性以及大鼠的乙醇偏好之间存在关联。对这三种行为的多重相关分析在HA大鼠中显示出显著值（r = -0.76，p <.01），在HB大鼠中也显示出显著值（r = -0.83，p <.01）。
对UChA和UChB大鼠杂交的这项研究表明，这三个参数是相关的，因为它们在F2代中聚集在一起。这一结果使我们推测，如果我们能够控制大鼠的急性耐受性发展，我们或许也能够控制它们的自愿乙醇摄入量。
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