Smolen A, Marks M J
Institute for Behavioral Genetics and Drug Abuse Research Center, University of Colorado, Boulder 80309-0447.
J Addict Dis. 1991;10(1-2):7-28. doi: 10.1300/J069v10n01_02.
We are using selective breeding to develop lines of mice which differ maximally in their responses to nicotine, and independent lines of mice which differ maximally in their responses to cocaine. The foundation population was the genetically heterogeneous HS mice. On day 1, baseline (saline injected) activity of each mouse was measured in an automated Y-maze over 3 minutes. On day 2, animals were tested for sensitivity to nicotine (0.75 mg/kg) in the same apparatus. A residual score, calculated from the regression of nicotine scores on saline scores for the whole population, was calculated for each animal. The most severely affected mice (lowest residual scores) were mated to form duplicate Nicotine-Depressed lines; the most stimulated mice (highest residual scores) were mated to form duplicate Nicotine-Activated lines. A random sampling of individuals was chosen without regard to residual scores for production of duplicate Control lines. Duplicate lines of mice activated and depressed by cocaine are being produced in an analogous fashion using 50 mg/kg cocaine as the test dose. Successful selective breeding for a drug-related trait provides clear evidence of a heritable component for that trait. These selected lines of mice will ultimately be used to study hypotheses involving genetic control of response to these drugs.
我们正在通过选择性育种培育对尼古丁反应差异最大的小鼠品系，以及对可卡因反应差异最大的独立小鼠品系。基础种群是基因异质的HS小鼠。在第1天，在自动Y迷宫中测量每只小鼠3分钟的基线（注射生理盐水）活动。在第2天，在同一装置中测试动物对尼古丁（0.75毫克/千克）的敏感性。根据整个种群尼古丁得分与生理盐水得分的回归计算出每只动物的残差分数。将受影响最严重的小鼠（最低残差分数）进行交配，形成重复的尼古丁抑制品系；将受刺激最大的小鼠（最高残差分数）进行交配，形成重复的尼古丁激活品系。不考虑残差分数，随机选择个体以产生重复的对照品系。使用50毫克/千克可卡因作为测试剂量，以类似方式培育对可卡因有激活和抑制作用的重复小鼠品系。成功地对与药物相关的性状进行选择性育种，为该性状的遗传成分提供了明确证据。这些选定的小鼠品系最终将用于研究涉及对这些药物反应的遗传控制的假说。
