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; 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（请参阅说明）： 吸毒者在抵抗与药物使用相关的刺激（提示）方面有很大的困难。这样的提示过于吸引他们的注意力，将它们吸引到毒品所在的地方，并激励持续的毒品寻求行为 - 即使面对表达停止使用毒品的渴望，也常常导致复发。 人们认为药物提示会因帕夫洛维亚调节而获得激励动机（“激励显着性”），因此以前中性刺激获得了条件刺激（CS）。 但是，在使用大鼠的临床前研究中，我们发现个体在将激励性的显着性奖励的程度上明显变化。奖励提示可以充当完全有效的CS，引起所有动物中有条件的反应（CR），但仅在某些动物中充当有效的激励刺激。 只有当奖励提示作为激励刺激时，他们才会吸引，煽动，挑衅，刺激和激励，从而导致潜在的适应不良行为。因此，我们假设个人容易归因于激励性显着性来奖励提示将在抵抗它们方面特别困难，并且特别容易受到成瘾式行为的影响。我们提出了一系列使用大鼠测试的临床前研究 这一假设，并确定这种“特质”与其他人认为赋予成瘾脆弱性的关系，包括做出“脉冲行动”的倾向。具体的研究解决了以下关键问题：（1）在任何药物经验之前都可以预测，哪些人会在哪些药物体验之前将诱因的显着性归因于毒品提示？ 为了奖励提示预测哪些人在给自我管理药物的机会扩大的机会时，他们容易发展成瘾行为？ （3）过去的药物经验是否会增加激励价值归因于药物提示的程度？ （4）Pavlovian刺激奖励学习所需的大脑区域是否在动物或不归因于激励显着性的动物中有所不同？ 这些研究有可能从根本上转移我们对成瘾的脆弱性的看法，并为靶向更好的干预措施指向道路。