CORE--MOUSE SELECTIVE BREEDING

核心——小鼠选育

• 批准号: 6563173
• 负责人: LAWRENCE LUMENG
• 金额: $ 13.07万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563173
• 关键词: alcohol dehydrogenase; alcoholic beverage consumption; alcoholism /alcohol abuse; aldehyde dehydrogenases; animal breeding; avoidance behavior; behavior test; behavioral /social science research tag; behavioral genetics; biomedical facility; cryopreservation; dopamine; enzyme activity; genetic markers; genetic models; genetic strain; high performance liquid chromatography; laboratory mouse; neuropharmacology; open field behavior; operant conditionings; phenotype; preference; serotonin

Progress in this Research Component has led to successful selective breeding and maintenance of a single pair of high and low alcohol- preferring mouse lines, i.e., HAP1 and LAP1. This accomplishment and our proposal to raise by mass selection two other pairs of high and low alcohol-preferring mouse lines (i.e., HAP2/LAP2 and HAP3/LAP3) can potentially produce an important research resource for the alcohol research community at large. A control line (CAP2) will be raised contemporaneously with the HAP2/LAP2. For the next five years, efforts will be devoted to the following: 1) To continue the development of the HAP1/LAP1 lines with plans to initiate inbreeding and cryopreservation of embryos when the selective breeding reaches maximal divergence and plateaus. 2) To repeat the above experiment by raising HAP2/LAP2 (with CAP2) and HAP3/LAP3. 3) To examine in the HAP/LAP lines certain selected correlated responses: locomotor activation and sensitizing effects of ethanol; baseline anxiety and the anxiolytic effects of ethanol; the development of acute tolerance to ethanol; and hedonic effects of ethanol as measured by conditioned taste aversion, operant oral self- administration and conditioned place preference. 4) To evaluate whether some of the putative quantitative trait loci reported by others can be confirmed in the HAP/LAP lines. 5) To measure in alcohol-naive HAP/LAP mice the steady state levels of serotonin (5-HT), dopamine, and met- enkephalin. 6) To evaluate the hypothesis forwarded by Badawy, i.e., alcohol preference in mice is due to higher serum corticosterone levels and thus higher hepatic tryptophan (Trp) pyrrolase activities and decreased brain contents of Trp and 5-HT. Most of the methods are already established in our Alcohol Research Center or will be carried out by Dr. Nicholas Grahame who has recently joined the Center.

该研究组成部分的进展导致了成功的选择性 一对高和低酒精的繁殖和维护 - 偏爱小鼠线，即HAP1和LAP1。 这个成就和我们的 提议通过质量选择提出另外两对高和低的提案 饮酒的小鼠系（即HAP2/LAP2和HAP3/LAP3）可以 潜在地为酒精生产重要的研究资源 整个研究社区。 将提高控制线（CAP2） 同时与HAP2/LAP2。 在接下来的五年中，努力 将致力于以下内容：1）继续发展 HAP1/LAP1线计划启动近亲和冷冻保存的计划 当选择性育种达到最大差异时，胚胎 高原。 2）通过提高hap2/lap2来重复上述实验（与 CAP2）和HAP3/LAP3。 3）在某些选定的某些选定的HAP/LAP线中检查 相关响应：运动激活和敏化作用 乙醇；基线焦虑和乙醇的抗焦虑作用；这 发展对乙醇的急性耐受性；和乙醇的享乐作用 按照条件味觉厌恶的衡量，操作者口头自我 管理和条件的地方偏好。 4）评估是否 其他人报告的一些推定的定量特质基因座可以是 在HAP/LAP线中确认。 5）测量酒精含量的HAP/LAP 小鼠5-羟色胺（5-HT），多巴胺和Met-的稳态水平 Enkephalin。 6）评估Bada​​wy转发的假设，即 小鼠的酒精偏好是由于血清皮质酮水平较高 因此，较高的肝色氨酸（TRP）吡咯酶活性和 TRP和5-HT的大脑含量减少。 大多数方法已经 在我们的酒精研究中心建立，或将由博士 尼古拉斯·格雷厄姆（Nicholas Grahame）最近加入了该中心。