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

项目总结(见说明)： 吸毒者很难抵抗与吸毒有关的刺激(暗示)。这样的线索不适当地吸引了他们的注意，把他们吸引到毒品所在的地方，并激发了持续的毒品寻找行为--即使面对明确的戒毒愿望，往往也会导致复发。 作为巴甫洛夫条件作用的结果，药物线索被认为获得了激励性动机特性(“激励性显著”)，即先前的中性刺激获得条件刺激(CS)特性。 然而，在用大鼠进行的临床前研究中，我们发现，在将激励突显归因于奖励线索的程度上，个体存在显著差异。奖励线索可以作为一种完全有效的CS，在所有动物中引发条件反应(CR)，但只在某些动物中起到强有力的激励刺激的作用。 只有当奖励暗示作为激励刺激时，它们才会吸引、煽动、挑衅、鞭策和激励，从而导致潜在的不适应行为。因此，我们假设，倾向于将激励突显归因于奖励线索的人将特别难以抵抗它们，并且特别容易发展成瘾行为。我们提出了一系列临床前研究，使用大鼠来测试 这一假设，并确定这一“特质”与其他被认为容易上瘾的人之间的关系，包括做出“冲动行为”的倾向。具体研究解决以下关键问题：(1)在任何吸毒经历之前，是否有可能预测哪些人会将激励性突出归因于药物提示？(2)将激励性突出归因于倾向的变化 用奖励线索来预测哪些人在被给予更多自我用药的机会时容易发展成瘾样行为？(3)过去吸毒的经历是否增加了药物线索对激励价值的贡献程度？(4)巴甫洛夫刺激-奖励学习所需的大脑区域在将激励突显归因于奖励线索的动物中是否存在差异？ 这些研究有可能从根本上改变我们对个体成瘾易感性的看法，并为更有针对性的干预指明方向。

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.