GWAS for Goal Versus Sign Tracking in Genetically Heterogeneous Rats

描述(由申请者提供)：我们的日常行为大多受与奖励相关的刺激(线索)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寻找和吸毒行为中的作用很感兴趣，因为对线索的反应可能是成瘾的重要组成部分。与奖励相关的暗示(条件刺激，CS)只有在被归因于激励激励属性(“激励突显”)的情况下才能有力地激励行为，从而获得充当激励刺激的能力。在近交系的SpragueDawley大鼠中，个体大鼠将激励突显归因于食物和药物线索的倾向存在很大差异。使用一种名为巴甫洛夫条件化方法(PCA)的行为范式，SD大鼠可被归类为手势跟踪器，这意味着它们将激励突显分配给线索(手势)或目标跟踪器，后者不将激励突显分配给线索。这份申请旨在利用一个绝佳的机会。作为正在进行的计划项目拨款的一部分，我们的合作者正在对数千只SD大鼠进行表型鉴定。它们为我们提供了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，然后进行全基因组关联研究。这将使我们能够识别在杂交后的Spraogue Dawley大鼠中观察到的PCA个体变异性背后的基因。因为我们不需要支付老鼠的住房或测试费用，这个项目非常便宜，但有可能为探索线索在塑造行为中的作用开辟全新的分子途径。这里提出的样本量(n=3,000)比我们在大鼠或小鼠身上所知的任何类似研究都要大，因此提供了突出的力量。

DESCRIPTION (provided by applicant): 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.