Genetic selection for high and low alcohol consumption in a limited-access paradigm
Genetic selection for high and low alcohol consumption in a limited-access paradigm
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DOI：
10.1111/j.1530-0277.2001.tb02168.x
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发表时间：
2001-11-01
影响因子：
3.2
通讯作者：
Harding, S
中科院分区：
文献类型：
--
作者：
Lê, AD;Israel, Y;Harding, S
背景：已有几个品系的大鼠因其饮酒量的差异而被培育，这是基于一种24小时/天提供酒精溶液的连续获取范式。然而，限制获取酒精溶液的范例(LAP)被广泛用于研究酒精消费的神经化学机制。在LAP中，酒精溶液的使用被限制在每天一小段时间。有证据表明，在持续饮酒和限制饮酒的情况下，饮酒的遗传决定可能存在差异。为此，我们在一圈的基础上进行了高酒精消耗和低酒精消耗(分别为HARF和LARIF)的选择性育种。采用家系内育种方法，选育出10个家系的HARF和LIBF品系。酒精溶液的使用被限制在每天20分钟。酒精以3%、6%和12%的w/v溶液提供。以12%阶段的平均酒精摄入量作为选择标准。结果：经过第六代选择后，HARF系大鼠在20分钟内平均饮酒量为1.2g/kg，而幼龄系大鼠平均饮酒量为0.6g/kg。在接下来的八代近亲交配中，酒精消费保持稳定。在连续饮酒模式中，HARF和LARF大鼠平均每天分别摄入5.5~7.0g/kg和1.0~2.0g/kg的酒精。遗传度估计为0.25。结论：这些发现表明在大腿上饮酒受遗传因素的影响。在圈内饮酒的差异也概括为连续饮酒。这些大鼠品系将对研究饮酒背后的遗传和神经化学机制非常有用。
Background: Several rat lines have been bred for their differences in alcohol consumption based on a continuous-access paradigm in which alcohol solution is available 24 hr/day. The limited-access paradigm (LAP), in which access to alcohol solution is restricted to a short period per day, however, has been used extensively to investigate the neurochemical mechanisms underlying alcohol consumption. There is evidence of possible differences in genetic determination of alcohol drinking in a continuous-versus limited-access condition. For these reasons, selective breeding for high- and low-alcohol consumption (HARF and LARF, respectively) based on a LAP was conducted.Methods: N/Nih rats were used as the breeding stock. A within-family breeding procedure was used to develop HARF and LARF lines with 10 families per line. Access to alcohol solution was restricted to 20 min/day. Alcohol was provided as 3%, 6% and 12% w/v solutions. Average intake of alcohol during the 12% phase was used as the selection criterion. Inbreeding began in the seventh generation.Results: After the sixth generation of selection, rats from the HARF line consumed an average of 1.2 g/kg, whereas rats from the LARF line consumed an average of 0.6 g/kg of alcohol during the 20-min access period. Alcohol consumption remained stable over the next eight generations of inbreeding. In the continuous-access-drinking paradigm, the HARF and LARF rats consumed an average of 5.5 to 7.0 g/kg and 1.0 to 2.0 g/kg of alcohol per day respectively. An estimated heritability of 0.25 was obtained.Conclusions: These findings indicate that alcohol drinking in the LAP is influenced by genetic factors. Differences in alcohol drinking in the LAP also generalize to continuous access drinking. These rat lines will be very useful for investigations into the genetic and neurochemical mechanisms underlying alcohol drinking.