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; 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都由与奖励相关的刺激（提示）控制；这些提示可以促进适应性或不良适应行为。我们对提示在促进药物寻求和吸毒行为中的作用感兴趣，因为对提示的反应可能是成瘾的重要组成部分。与奖励（条件刺激，CSS）相关的提示只有在将激励动机特性（“激励显着性”）归因时，才能有力地激励行为，从而获得充当激励刺激的能力。在杂种Sprague Dawley大鼠中，单个大鼠的倾向有很大的差异，将激励显着性归因于食物和药物提示。使用称为Pavlovian条件方法（PCA）的行为范式，Sprague Dawley大鼠可以被归类为标志跟踪器，这意味着它们为提示（标志）或目标跟踪器分配了激励性显着性，这不会为提示分配激励性的显着性。该申请旨在利用一个出色的机会。作为正在进行的计划项目赠款的一部分，我们的合作者正在表现出数千名Sprague Dawley老鼠。他们为我们提供表型数据和尾巴作为DNA的来源。当前的建议旨在基因于这些样本，然后进行全基因组关联研究。这将使我们能够确定在Sprague Dawley大鼠中观察到的PCA个体变异性的基因。因为我们不需要支付住房或测试大鼠的费用，所以该项目非常便宜，但有可能为探索提示在塑造行为中的作用而打开全新的分子途径。这里提出的样本量（n = 3,000）大于我们在大鼠或小鼠中所知道的任何类似研究，因此提供了出色的功率。