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

• 批准号: 7851257
• 负责人: Shelly Beth Flagel
• 金额: $ 7.73万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 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/7851257
• 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

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）：虽然有些人能够随便使用药物而不会干扰他们的日常活动，但其他人会上瘾，无法将他们的思想和行为转移到毒品和与药物相关的刺激中。这些个体差异的基础因素尚不清楚，但是一个合理的解释是成瘾责任中的个体差异与奖励相关的线索控制行为的程度有关。可以使用Pavlovian调节程序在实验室中研究与奖励相关刺激获得对行为的控制的能力。当离散提示与收到奖励的可靠配对时，它不仅可以作为奖励的预测指标，而且还可以引起复杂的情感和动机状态。因此，对于某些动物，目标追踪者而言，与奖励相关的提示仅作为一种预测因子，引发了针对奖励交付位置的方法。对于其他人来说，签名人的提示具有动机价值，引起的方法和针对提示的完整行为。签名跟踪行为被认为反映了激励显着性对奖励相关线索的增强归因，因此可能与研究成瘾行为和复发尤其重要。然后，工作的假设是，签名者可以代表增加脆弱性成瘾的人。而目标追踪者可以代表那些对疾病有弹性的人。为了检验这一假设，我们将根据寻求新颖的特征选择性地繁殖出独特的遗传动物模型鼠，但已知以与成瘾相关的许多特征有所不同。育高响应者大鼠（BHR）主要是签名轨道，展示了与食品和药物（可卡因）奖励相关的提示方法；繁殖的低响应器大鼠（BLR）几乎完全是目标追踪者，接近奖励交付的位置。杂交中间响应者（BIR）的行为与商业大鼠的行为相似，几乎相等的概率是发展目标跟踪或签名跟踪行为。利用所有这三条线条将在人群中提供连续性，使我们能够研究各种特征（例如寻求新颖性，签名追踪）和成瘾责任之间的关系。将获得以下药物滥用脆弱性的指标：i）在长时间（5小时）可卡因自我管理会议上升级药物摄入量； ii）当药物不再可用时，吸毒行为的持久性； iii）抵抗灭绝；和iv）在30天的禁欲期之后，提示引起的恢复（即复发）。从这些成瘾责任的衡量标准中，将确定签名轨道的大鼠是否更容易对成瘾相对于该目标轨道的大鼠过渡。此外，选择性繁殖的大鼠线的使用为未来研究提供了巨大的潜力，以研究与成瘾行为相关的特征的遗传，分子和行为前提。公共卫生相关性：拟议的项目将检查与奖励相关的线索控制行为的程度上是否与药物滥用脆弱性有关。利用有选择的大鼠线，这些研究可能被证明在理解有助于成瘾发展的心理，神经生物学和遗传机制方面非常有用。此外，提出的动物模型可能使我们能够确定某些人容易成瘾的人以及保护他人免受疾病的原因是什么。