Human sign-tracking: Individual differences in motivational value of reward cues

项目总结 为了预防和治疗药物使用，重要的是要确定谁有上瘾的风险及其原因。这样做的目的是 B/START奖是为了开发一种对成瘾风险因素的人类衡量标准，以前只有 在实验动物身上被胺化。具体地说，最近的临床前研究结果表明，将PAR- 与奖励相关的线索(即视觉、气味或物体)具有特别强的激励价值，有可能 上瘾。在动物身上，这种倾向表现为对线索的强迫接近，或与重新定位有关的“标志”。 沃德，一种被称为“手势跟踪”的行为。重要的是，记号跟踪的动物在实验室里表现出上瘾的倾向- 吸毒和复发的关系模型。手势跟踪还与冲动行为相关，这是一种已知的风险因素- 托尔治疗上瘾。最后，手势跟踪是基于大脑多巴胺系统的根本差异，一种 成瘾的关键神经底物。然而，应用这一极有希望的行为指标存在一个关键障碍- 预测和理解人类成瘾的成瘾风险因素：尚无有效的人类测量方法 这一趋势。这项B/START赠款的目标是开发一种敏感的行为测量方法，即 我们已经开发了一种程序来测量与食物再分配配对的线索的反应。 人类的病房。该程序量化了个体在将激励价值附加到 使用包括主观、心理生理学和手势的综合测量的提示(即“人类手势跟踪 对线索吸引的行为指数。在目标1中，我们将进行一项初步研究，以完善这项新措施，在 哪40名健康的成年人将在一种情况下执行人类手势跟踪任务，我们将调整参数- TERS以优化调节和测量。然后在目标2中，我们将进行一项验证性研究，其中 健康的成年人将参与一项为期两个阶段的研究，使用的是人类手势跟踪的最终衡量标准。在每个 在会议期间，他们将完成手势跟踪任务以及对冲动行为的有效衡量。在 这个单一的高效设计，我们将在两个调理阶段检查我们测量的稳定性(目标2a)。 以及它与冲动行为的收敛有效性(目标2b)。我们的中心假设是，在人类身上，就像在老鼠身上一样， 手势跟踪将是一种稳定的个体差异，与冲动行为的倾向相关。这个 拟议的研究意义重大，因为我们预计它将验证一种新颖的、直接的翻译行为 衡量上瘾风险的一个有希望的指标。这有可能在几个方面推动该领域的发展， 包括改进对成瘾风险的预测，提供有关可能调解的行为的新信息 多巴胺异常与成瘾临床症状之间的关系，并提示新的行为靶点 进行干预。这项拟议的研究具有创新性，因为这是首次尝试将这一特征量化 人类。这笔赠款将构成未来一系列方向的基础，包括使用VALI程序-- 在这里用来预测与成瘾相关的结果，如对药物的急性反应和线索诱导的复发， 以及研究人类手势跟踪与多巴胺功能之间的关系。

PROJECT SUMMARY To prevent and treat drug use it is important to identify who is at risk for addiction and why. The goal of this B/START award is to develop a human measure of a risk factor for addiction that has previously only been ex- amined in laboratory animals. Specifically, recent preclinical findings suggest that individuals who attach par- ticularly strong motivational value to cues (i.e. sights, smells or objects) associated with reward are at risk for addiction. In animals this tendency manifests as compulsive approach to cues, or "signs", associated with re- ward, a behavior called "sign-tracking". Importantly, animals that sign-track show addictive tendencies in labo- ratory models of drug-taking and relapse. Sign-tracking also correlates with impulsive action, a known risk fac- tor for addiction. Finally, sign-tracking is based in fundamental differences in the brain's dopamine system, a key neural substrate of addiction. Yet there is a critical barrier to applying this highly promising behavioral indi- cator of addiction risk to predicting and understanding human addiction: There is no validated human measure of this tendency. The objective of this B/START grant is to develop a sensitive behavioral measure of "sign- tracking" in humans. We have developed a procedure that measures responses to cues paired with food re- ward in humans. The procedure quantifies individual differences in the tendency to attach motivational value to cues (i.e. "human sign-tracking") using a composite measure consisting of subjective, psychophysiological and behavioral indices of attraction to cues. In Aim 1 we will conduct a pilot study to refine this novel measure, in which 40 healthy adults will perform our human sign-tracking task on one occasion and we will adjust parame- ters to optimize conditioning and measurement. Then in Aim 2 we will conduct a validation study in which 100 healthy adults will participate in a two-session study using the final measure of human sign-tracking. At each session, they will complete the sign-tracking task as well as a validated measure of impulsive actions. Within this single efficient design we will examine stability of our measure over two sessions of conditioning (Aim 2a) and its convergent validity with impulsive actions (Aim 2b). Our central hypothesis is that in humans, as in rats, sign-tracking will be a stable individual difference that correlates with a tendency towards impulsive action. The proposed research is significant because we expect it will validate a novel and directly translational behavioral measure of a promising indicator of addiction risk. This has the potential to advance the field in several ways, including improving prediction of addiction risk, providing novel information about behaviors that may mediate between dopamine abnormalities and clinical symptoms of addiction, and suggesting new behavioral targets for intervention. The proposed research is innovative because this is the first attempt to quantify this trait in humans. This grant will form the foundation of a series of future directions, including using the procedure vali- dated here to predict addiction-relevant outcomes such as acute responses to drugs and cue-induced relapse, and examination of the relationship of sign-tracking to dopamine functioning in humans.