GWAS for goal versus sign tracking in genetically heterogeneous rats

项目总结/摘要 我们的许多日常行为都受到与奖励相关的刺激（线索）的控制;这些线索可以 促进适应性或适应不良行为。我们感兴趣的是线索在促进药物 寻求和吸毒行为，因为对线索的反应可能是成瘾的重要组成部分。 与奖励相关的线索（条件刺激，CS）只有在归因时才能有力地激励行为 具有激励性动机属性（“激励突出性”），从而获得作为激励的能力 刺激。在远系繁殖的Sprague道利大鼠中，个体大鼠的倾向存在很大差异， 将激励显著性归因于食物和药物线索。使用一种叫做巴甫洛夫条件反射的行为范式 在主成分分析（PCA）中，Sprague道利大鼠可被归类为信号追踪者，这意味着它们分配激励 显著性的线索（标志）或目标跟踪器，不分配激励显着性的线索。 此应用程序旨在利用一个出色的机会。作为一个正在进行的项目的一部分， 我们的合作者正在对几千只Sprague道利大鼠进行表型分析。他们为我们提供 用表型数据和尾巴作为DNA的来源。目前的建议旨在对这些样本进行基因分型， 然后进行全基因组关联研究。这将使我们能够确定基因的基础， 在远系繁殖的Sprague道利大鼠中观察到PCA的个体差异。因为我们不需要为 尽管这个项目的成本非常低，但它有可能成为一个开放的市场。 探索线索在塑造行为中的作用的全新分子途径。样本量 本文提出的（n= 3，000）比我们所知道的在大鼠或小鼠中进行的任何类似研究都要大，因此提供了 杰出的力量

PROJECT SUMMARY/ABSTRACT Much of our daily behavior is controlled by stimuli (cues) associated with rewards; these cues can promote either adaptive or maladaptive behavior. We are interested in the role of cues in promoting drug seeking and drug taking behavior because the response to cues may be an essential component of addiction. Cues associated with rewards (conditional stimuli, CSs) powerfully motivate behavior only if they are attributed with incentive motivational properties ("incentive salience"), and thus acquire the ability to act as incentive stimuli. Among outbred Sprague Dawley rats there is large variation in the propensity of individual rats to attribute incentive salience to food and drug cues. Using a behavioral paradigm called Pavlovian Conditioned Approach (PCA), Sprague Dawley rats can be categorized as sign trackers, meaning that they assign incentive salience to the cue (sign) or goal trackers, which do not assign incentive salience to the cue. This application seeks to take advantage of an outstanding opportunity. As part of an ongoing program project grant, our collaborators are phenotyping several thousand Sprague Dawley rats. They are providing us with phenotypic data and tails as a source of DNA. The current proposal seeks to genotype these samples and then to perform a genome-wide association study. This will allow us to identify genes that underlie the individual variability in PCA observed among outbred Sprague Dawley rats. Because we do not need to pay for the cost of housing or testing the rats, this project is extremely inexpensive yet has the potential to open up completely new molecular avenues for the exploration of the role of cues in shaping behavior. The sample size proposed here (n=3,000) is larger than any similar study that we are aware of in rats or mice and thus provides outstanding power.