GWAS for goal versus sign tracking in genetically heterogeneous rats

GWAS 用于遗传异质性大鼠的目标与体征追踪

• 批准号: 8623562
• 负责人: ABRAHAM A PALMER
• 金额: $ 20.63万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2016-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8623562
• 关键词: Accounting; Address; Animal Model; Animals; Area Analyses; Attention; Behavior; Behavioral; Behavioral Paradigm; Breeding; Characteristics; Complex; Congenic Strain; Cues; DNA; Data; Drug abuse; Drug usage; Emerging Technologies; Failure; Food; Functional disorder; Funding; Future; Gene Frequency; Generations; Genes; Genetic; Genetic Determinism; Genotype; Goals; Grant; Housing; Human; Incentives; Individual; Individual Differences; Learning; Linkage Disequilibrium; Measures; Methods; Minor; Modeling; Molecular; Mus; Pattern; Pharmaceutical Preparations; Phenotype; Population; Population Heterogeneity; Procedures; Production; Program Research Project Grants; Property; Quantitative Trait Loci; Rattus; Recombinant Inbred Strain; Relapse; Rewards; Role; SNP genotyping; Sample Size; Sampling; Scheme; Self Administration; Shapes; Source; Sprague-Dawley Rats; Stimulus; Structure; Tail; Techniques; Testing; Tissues; Variant; Work; addiction; base; classical conditioning; conditioning; cost; drug development; drug seeking behavior; follow-up; genome wide association study; insight; interest; motivated behavior; mutant; new therapeutic target; novel; programs; public health relevance; response; stem; trait

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.

项目摘要/摘要 我们的大部分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中的作用感兴趣 寻求和吸毒行为是因为对提示的反应可能是成瘾的重要组成部分。 与奖励相关的提示（有条件刺激，CSS）仅在归因于行为的情况下才能有力激励行为 具有激励动机的特性（“激励显着性”），从而获得充当激励的能力 刺激。在杂种Sprague Dawley大鼠中，单个大鼠倾向的差异很大 将激励性显着性归因于食品和药物提示。使用称为Pavlovian条件的行为范式 方法（PCA），Sprague Dawley Rats可以归类为标志跟踪器，这意味着他们分配了激励措施 对提示（标志）或目标跟踪器的显着性，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的一部分 Grant项目，我们的合作者正在表现出数千名Sprague Dawley老鼠。他们正在为我们提供 以表型数据和尾巴为DNA来源。当前的提案旨在基因于这些样本，并 然后进行全基因组关联研究。这将使我们能够确定基于 在杂种Sprague Dawley大鼠中观察到PCA的个体变异性。因为我们不需要付费 住房或测试大鼠的成本，该项目非常便宜，但有可能开放 全新的分子途径，用于探索线索在塑造行为中的作用。样本量 这里提出的（n = 3,000）比我们在大鼠或小鼠中知道的任何类似研究都要大 出色的力量。