Project 1: Attribution of Incentive Salience to Reward Cues: Implications for Add

项目 1：奖励线索的激励显着性的归因：对 Add 的影响

• 批准号: 8311876
• 负责人: Terry E. Robinson
• 金额: $ 28.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311876
• 关键词: Address; Animal Model; Animals; Attention; Behavior; Behavior Control; Behavioral; Brain region; Cocaine; Conflict (Psychology); Cues; Data; Development; Drug Addiction; Drug usage; Exposure to; Extinction (Psychology); Food; Goals; Incentives; Individual; Individual Differences; Instruction; Intervention; Learning; Location; Modeling; Neurobiology; Nicotine; Opioid; Outcome; Paper; Persons; Pharmaceutical Preparations; Phenotype; Pre-Clinical Model; Procedures; Property; Psychological reinforcement; Public Health; Publishing; Rattus; Relapse; Rewards; Risk Factors; Self Administration; Self-Administered; Series; Stimulus; Stress; Symptoms; System; Testing; Thinking; United States; Variant; addiction; base; classical conditioning; drug addict; drug of abuse; drug seeking behavior; experience; preclinical study; psychologic; reinforcer; relating to nervous system; research study; response; trait

PROJECT SUMMARY (See instructions): Addicts have great difficulty resisting stimuli (cues) that have been associated with drug use. Such cues unduly attract their attention, draw them to locations where drugs are located and motivate continued drug seeking behavior - often leading to relapse even in the face of an expressed desire to discontinue drug use. Drug cues are thought to acquire incentive motivational properties ("incentive salience") as a consequence of Pavlovian conditioning, whereby previously neutral stimuli acquire conditional stimulus (CS) properties. However, in preclinical studies using rats we have discovered that individuals vary markedly in the extent to which they attribute incentive salience to reward cues. A reward cue may act as a perfectly effective CS, evoking a conditional response (CR) in all animals, but function as a potent incentive stimulus only in some. Only if reward cues act as incentive stimuli do they come to attract, incite, provoke, spur and motivate, leading to potentially maladaptive behavior. We hypothesize, therefore, that individuals prone to attribute incentive salience to reward cues will have particular difficulty resisting them and will be especially vulnerable to develop addiction-like behavior. We propose a series of preclinical studies using rats to test this hypothesis, and to determine the relationship between this "trait", and others thought to confer vulnerability to addiction, including a propensity to make "impulsive actions'. Specific studies address the following key questions: (1) Is it possible to predict, prior to any drug experience, which individuals will attribute incentive salience to a drug cue? (2) Does variation in the propensity to attribute incentive salience to reward cues predict which individuals are susceptible to develop addiction-like behavior when they are given extended opportunity to self-administer drugs? (3) Does past experience with drugs increase the degree to which incentive value is attributed to drug cues? (4) Do the brain regions necessary for Pavlovian stimulus-reward learning differ in animals that do or do not attribute incentive salience to reward cues? These studies have the potential to fundamentally shift how we think about individual vulnerability to addiction, and point the way for better-targeted interventions.

项目摘要（参见说明）： 成瘾者很难抵抗与吸毒有关的刺激（暗示）。这些线索过度地吸引了他们的注意力，将他们吸引到毒品所在的地方，并激发他们继续寻求毒品的行为——即使在明确表示希望停止吸毒的情况下，往往也会导致旧瘾复发。 药物线索被认为是巴甫洛夫条件作用的结果，从而获得激励动机特性（“激励显着性”），从而使先前的中性刺激获得条件刺激（CS）特性。 然而，在使用大鼠进行的临床前研究中，我们发现个体将激励显着性归因于奖励线索的程度存在显着差异。奖励提示可以作为一种完全有效的 CS，在所有动物中引起条件反应 (CR)，但仅在某些动物中充当有效的激励刺激。 只有当奖励线索充当激励刺激时，它们才会吸引、煽动、激怒、刺激和激励，从而导致潜在的适应不良行为。因此，我们假设，倾向于将激励显着性归因于奖励线索的个体将特别难以抵制它们，并且特别容易出现类似成瘾的行为。我们提出了一系列使用大鼠来测试的临床前研究 的假设，并确定这种“特征”与其他被认为容易上瘾的特征之间的关系，包括做出“冲动行为”的倾向。具体研究解决了以下关键问题：（1）是否有可能在任何吸毒经历之前预测哪些人会将激励显着性归因于药物提示？（2）归因于激励显着性的倾向是否存在变化？ 奖励线索可以预测哪些人在获得更多自我用药机会时容易出现成瘾样行为？ (3) 过去的吸毒经验是否会增加吸毒线索的激励价值程度？ (4) 在将激励显着性归因于奖励线索或不将激励显着性归因于奖励线索的动物中，巴甫洛夫刺激奖励学习所需的大脑区域是否有所不同？ 这些研究有可能从根本上改变我们对个人成瘾脆弱性的看法，并为更有针对性的干预措施指明道路。