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

项目总结（见说明）： 成瘾者很难抵抗与吸毒有关的刺激（线索）。这些线索不适当地吸引了他们的注意力，将他们吸引到毒品所在的地方，并促使他们继续寻求毒品的行为-即使在他们明确表示希望停止吸毒的情况下，也往往导致复吸。 药物线索被认为是获得激励动机属性（“激励显着性”）作为巴甫洛夫条件反射的结果，其中先前中性刺激获得条件刺激（CS）属性。 然而，在使用大鼠的临床前研究中，我们发现个体在将激励显着性归因于奖励线索的程度上存在显着差异。奖励线索可以作为一个完全有效的CS，唤起所有动物的条件反应（CR），但功能作为一个强有力的激励刺激只有在一些。 只有当奖励线索作为激励刺激，他们来吸引，煽动，挑衅，刺激和激励，导致潜在的适应不良行为。因此，我们假设，倾向于将激励显著性归因于奖励线索的个体将特别难以抵制它们，并且特别容易发展成成瘾行为。我们提出了一系列的临床前研究使用大鼠测试 这一假设，并确定这一“特点”之间的关系，和其他人认为赋予脆弱性成瘾，包括倾向于作出“冲动行为”。具体的研究解决了以下关键问题：（1）是否有可能预测，在任何药物的经验，哪些人会归因于激励显着性的药物线索？(2)归因于激励显著性的倾向的变化 奖励线索预测哪些个体在被给予延长的自我管理药物的机会时容易产生成瘾样行为？(3)过去的药物经验是否会增加药物线索的激励价值？(4)在将激励显著性归因于奖励线索或不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方向。

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.