GWAS for goal versus sign tracking in genetically heterogeneous rats

项目摘要/摘要 我们日常的许多行为都受到与奖励相关的刺激(线索)的控制；这些线索可以 促进适应或不适应行为。我们对线索在促进药物方面的作用很感兴趣 寻求和吸毒行为，因为对暗示的反应可能是上瘾的重要组成部分。 与奖励相关的暗示(条件刺激，CSS)只有在被归因于奖励的情况下才能有力地激励行为 具有激励激励特性(“激励突显”)，从而获得作为激励的能力 刺激物。在近交系Spraogue Dawley大鼠中，单个大鼠的倾向存在很大差异 将激励的重要性归因于食物和药物的暗示。使用一种称为巴甫洛夫条件反射的行为范式 接近(PCA)，SpragueDawley大鼠可被归类为手势跟踪器，这意味着它们分配激励 提示(手势)或目标跟踪器的显著程度，它们不会将激励显著程度分配给提示。 这份申请旨在利用一个绝佳的机会。作为正在进行的计划的一部分 项目拨款后，我们的合作者正在对数千只Spraogue Dawley大鼠进行表型鉴定。他们正在为我们提供 以表型数据和尾巴作为DNA的来源。目前的提议寻求对这些样本进行基因分型，并 然后进行全基因组关联研究。这将使我们能够识别构成 观察到近交系SD大鼠在PCA中的个体差异。因为我们不需要付钱 居住或测试老鼠的成本，这个项目非常便宜，但有开放的潜力 探索线索在塑造行为中的作用的全新分子途径。样本大小 这里提出的(n=3,000)比我们所知的任何类似的大鼠或小鼠研究都要大，因此提供了 超凡的力量。

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.