Individual Differences in Incentive Salience Attribution: Relevance to Addiction

激励显着归因的个体差异：与成瘾的相关性

基本信息

批准号：
7738177
负责人：
Shelly Beth Flagel
金额：
$ 7.45万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7738177
关键词：
Abstinence Addictive Behavior Aggressive behavior Animal Model Animals Anxiety Behavior Behavior Control Behavioral Breeding Characteristics Cocaine Complex Conduct Disorder Consummatory Behavior Cues Data Development Diagnosis Dimensions Disease Disinhibition Drug Addiction Drug Delivery Systems Drug abuse Drug usage Emotional Ensure Esthesia Exhibits Experimental Designs Exposure to Extinction (Psychology)Food Future Genetic Goals Human Impulsivity Incentives Individual Individual Differences Intake Laboratories Learning Life Location Measures Mediating Modeling Molecular Genetics Neurobiology Outcome Pattern Pharmaceutical Preparations Phenotype Population Probability Procedures Rattus Regression Analysis Relapse Relative (related person)Resistance Rewards Risk-Taking Role Self Administration Stimulus Substance abuse problem Testing Thinking Time Withdrawal Work abstracting addiction base classical conditioning craving drug seeking behavior externalizing behavior falls indexing motivated behavior psychologic public health relevance reinforcer response trait

项目摘要

DESCRIPTION (provided by applicant): While some individuals are able to casually use a drug without it interfering with their day-to-day activities, others become addicted, unable to shift their thoughts and actions away from drugs and drug-associated stimuli. The factors underlying these individual differences are not yet known, but one plausible explanation is that individual differences in addiction liability are related to the extent to which reward-related cues come to control behavior. The ability of reward-related stimuli to gain control over behavior can be studied in the laboratory using Pavlovian conditioning procedures. When a discrete cue is reliably paired with the receipt of a reward, it not only serves as a predictor of reward, but can also elicit complex emotional and motivational states. Thus, for some animals, goal-trackers, the reward-related cue serves merely as a predictor, eliciting approach directed toward the location of reward delivery; and for others, sign-trackers, the cue attains motivational value, eliciting approach and consummatory behavior directed towards the cue. Sign-tracking behavior is thought to reflect enhanced attribution of incentive salience to reward-related cues and may therefore be especially relevant to the study of addictive behavior and relapse. The working hypothesis then is that sign-trackers may represent individuals with increased vulnerability to addiction; whereas goal-trackers may represent those that are resilient to the disorder. To test this hypothesis, we will utilize a unique genetic animal model-rats selectively bred on the basis of a novelty-seeking trait but known to diverge on a number of traits relevant to addiction. Bred high-responder rats (bHR) are primarily sign-trackers, exhibiting approach to cues associated with both food and drug (cocaine) reward; and bred low-responder rats (bLR) are almost exclusively goal-trackers, approaching the location of reward delivery. Cross-bred intermediate responders (bIR) behave similarly to commercial rats, with almost equal probability of developing either goal-tracking or sign-tracking behavior. Utilizing all three of these lines will provide a continuum in the population, enabling us to examine the relationship between various traits (e.g. novelty-seeking, sign-tracking) and addiction liability. The following indices of substance abuse vulnerability will be obtained: I) escalation of drug intake during prolonged (5-hr) cocaine self-administration sessions; II) the persistence of drug-taking behavior when the drug is no longer available; III) resistance to extinction; and IV) cue-induced reinstatement (i.e. relapse) following a 30-day abstinence period. From these measures of addictive liability it will be determined whether rats that sign-track are more susceptible to the transition to addiction relative to rats that goal-track. Moreover, the use of the selectively bred rat lines provides enormous potential for future studies to investigate the genetic, molecular and behavioral antecedents to traits relevant to addictive behavior. PUBLIC HEALTH RELEVANCE: The proposed project will examine whether individual differences in the extent to which reward-related cues come to control behavior are related to substance abuse vulnerability. Utilizing selectively bred rat lines, these studies may prove to be very informative in understanding the psychological, neurobiological, and genetic mechanisms that contribute to the development of addiction. Moreover, the proposed animal model may allow us to determine what renders some individuals susceptible to addiction and what protects others from developing the disorder.

描述（由申请人提供）：虽然有些人能够随意使用药物而不干扰他们的日常活动，但其他人却上瘾了，无法将他们的思想和行为从药物和与药物相关的刺激中转移开。这些个体差异背后的因素尚不清楚，但一种合理的解释是，成瘾倾向的个体差异与奖励相关线索控制行为的程度有关。可以在实验室中使用巴甫洛夫调节程序来研究与奖励相关的刺激获得对行为的控制的能力。当离散线索与奖励的接收可靠地配对时，它不仅可以作为奖励的预测因子，而且还可以引发复杂的情绪和动机状态。因此，对于一些目标追踪动物来说，与奖励相关的线索仅仅充当预测因子，引发针对奖励递送位置的方法；对于其他人（即信号跟踪者）来说，提示获得了激励价值，引发了针对提示的接近和完美行为。符号跟踪行为被认为反映了奖励显着性对奖励相关线索的增强归因，因此可能与成瘾行为和复发的研究特别相关。有效的假设是，体征追踪器可能代表了更容易上瘾的个体。而目标追踪者可能代表那些对这种疾病有抵抗力的人。为了检验这一假设，我们将利用一种独特的遗传动物模型——基于寻求新奇特征而选择性培育的老鼠，但已知它们在许多与成瘾相关的特征上存在分歧。繁殖的高反应大鼠（bHR）主要是信号追踪者，表现出对与食物和药物（可卡因）奖励相关的线索的方法；繁殖的低反应大鼠（bLR）几乎完全是目标追踪器，接近奖励递送的位置。杂交中间反应者（bIR）的行为与商业老鼠相似，发展目标跟踪或信号跟踪行为的可能性几乎相同。利用所有这三个线将为人群提供一个连续体，使我们能够检查各种特征（例如寻求新奇、信号跟踪）和成瘾倾向之间的关系。将获得以下药物滥用脆弱性指数： I) 在长时间（5 小时）可卡因自我给药过程中药物摄入量增加； II) 当药物不再可用时，吸毒行为持续存在； III) 抵抗灭绝； IV) 30 天禁欲期后提示诱导的恢复（即复发）。根据这些成瘾倾向的测量，将确定手语追踪的老鼠是否比目标追踪的老鼠更容易成瘾。此外，选择性繁殖的大鼠品系的使用为未来研究与成瘾行为相关特征的遗传、分子和行为前因提供了巨大的潜力。公共卫生相关性：拟议项目将研究奖励相关线索控制行为程度的个体差异是否与药物滥用脆弱性有关。利用选择性培育的大鼠系，这些研究可能会为理解导致成瘾发展的心理、神经生物学和遗传机制提供非常丰富的信息。此外，所提出的动物模型可以让我们确定是什么使某些个体容易上瘾，以及什么可以保护其他人免受这种疾病的影响。