GWAS for Goal Versus Sign Tracking in Genetically Heterogeneous Rats

GWAS 用于遗传异质大鼠的目标与体征跟踪

• 批准号: 9196162
• 负责人: ABRAHAM A PALMER
• 金额: $ 11.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9196162
• 关键词: GWAS; Goal; Versus; Sign; Tracking

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.

描述（由申请人提供）：我们的许多日常行为是由与奖励相关的刺激（线索）控制的;这些线索可以促进适应或适应不良行为。我们对线索在促进药物寻求和药物服用行为中的作用感兴趣，因为对线索的反应可能是成瘾的重要组成部分。与奖励相关的线索（条件刺激，CS）只有当它们被归因于激励动机属性（“激励显著性”）时才能有力地激励行为，从而获得作为激励刺激的能力。在远系繁殖的Sprague道利大鼠中，个体大鼠将激励显著性归因于食物和药物线索的倾向存在很大差异。使用一种称为巴甫洛夫条件方法（PCA）的行为范式，Sprague道利大鼠可以被归类为符号追踪者，这意味着它们将激励显着性分配给线索（符号）或目标追踪者，而不是将激励显着性分配给线索。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计划项目赠款的一部分，我们的合作者正在对数千只Sprague道利大鼠进行表型分析。他们为我们提供了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上观察到的PCA远交Sprague道利大鼠之间的个体差异。因为我们不需要支付饲养或测试大鼠的费用，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。本文提出的样本量（n= 3，000）大于我们所知的在大鼠或小鼠中进行的任何类似研究，因此提供了出色的功效。