A Translational Model of Mood-Based Drug Abuse

描述(由申请人提供)：紧迫感，或基于情绪的皮疹行为，是人类临床文献中定义的冲动的四个方面之一(Whiteside&Lynam，2001；Cyders，Smith，Spillane，Fischer，Annus，&Peterson，2007)。紧迫感的动物模型可能会进一步了解特定大脑系统在基于情绪的皮疹行动中所起的作用。通过操纵奖励期望，可以在实验室大鼠(Gipson，Zentall和Bardo，正在准备)中测量行为结果(如强化省略效应，或ROE)。Gipson等人。试图利用大鼠的可操作性任务来开发一种可操作性的动物紧迫感模拟。动物接受一种最初的巴甫洛夫成分，在这种成分中，条件刺激(关键光)与一个蔗糖颗粒的输送相匹配。随后是一个末端的可操作组件，动物能够重复完成一个蔗糖颗粒的固定比率(FR)-10强化计划。在巴甫洛夫成分试验(遗漏试验)中，很少有蔗糖颗粒被交付。在两种试验类型上都测量了应答率--遗漏试验期间的应答率增加(ROE效应)。这一程序使紧急程度的个体差异得以量化。第一项拟议的研究旨在检验省略预期的非药物奖励(蔗糖丸)对大鼠d-苯丙胺自我给药的影响。第二组拟议的研究旨在通过在人类中使用模拟操作任务来检查紧迫感的个体差异，并确定这些个体差异是否反映了UPPS个性量表上的紧迫感分数，以检验ROE的跨物种共性。使用上述非人类动物程序的一种变体，个体将在意外遗漏奖励后接受应答率测试。货币奖励将在两项人体研究中用作初始组成部分中的非或有预期奖励。受试者将被允许在终端组件中的FR-100时间表上点击计算机鼠标，并将获得金钱(研究2a)或积分，可以换取d-苯丙胺胶囊(研究2b)。为了更好地了解如何降低人类基于情绪的皮疹行为的风险，量化个体在紧迫感上的差异是很重要的。虽然关于人类紧迫感涉及的神经系统的信息很少，但一个有效的皮疹行为动物模型将为更好地研究这些系统提供一个基础。如果更好地了解导致紧迫感的神经行为原因，可以更有效地降低风险，如果能够开发出专门针对这些与紧迫感有关的大脑区域的药物，易感人群的冲动可能会减少。 公共卫生相关性：众所周知，冲动是包括药物滥用在内的各种负面健康相关行为的风险因素。该项目将评估老鼠和人类受试者的冲动行为模型，以确定其与人格问卷的相关性，后者通常用于评估人类的冲动。这项工作将增进我们对冲动行为和药物滥用的神经机制的基础知识。

DESCRIPTION (provided by applicant): Urgency, or mood-based rash action, is one of four facets of impulsivity defined in human clinical literature (Whiteside & Lynam, 2001; Cyders, Smith, Spillane, Fischer, Annus, & Peterson, 2007). An animal model of urgency may allow further understanding of the role of specific brain systems in mood-based rash action. By manipulating reward expectancy, behavioral outcomes (such as a reinforcement omission effect, or ROE) can be measured in laboratory rats (Gipson, Zentall, & Bardo, in preparation). Gipson et al. sought to develop an operant animal analogue of urgency using an operant task in rats. Animals received an initial Pavlovian component in which a conditioned stimulus (a key light) was paired with the delivery of one sucrose pellet. A terminal, operant component followed in which animals were able to repeatedly complete a fixed-ratio (FR)-10 schedule of reinforcement for one sucrose pellet. Infrequently, no sucrose pellet was delivered in the Pavlovian component (omission trials). Response rates were measured on both trial types - rates were increased during omission trials (an ROE effect). This procedure allowed individual differences in level of urgency to be quantified. The first proposed study is designed to examine the effects of omission of expected non-drug reward (sucrose pellets) on d-amphetamine self-administration in rats. The second proposed set of studies is designed to examine the cross-species generality of the ROE by examining individual differences in urgency using an analog performance task in humans, and to determine if these individual differences reflect urgency scores on the UPPS personality scale. Using a variation of the nonhuman animal procedure described above, individuals will be tested for response rates following unexpected omission of reward. Monetary reward will be used in both human studies as the non-contingent expected reward in the initial component. Subjects will be allowed to click a computer mouse on a FR-100 schedule in a terminal component, and will receive money (study 2a) or points that can be exchanged for capsules of d-amphetamine (study 2b). To better understand how to reduce risk for mood-based rash action in humans, it is important to quantify individual differences in urgency. While there is little information on the neural systems involved in human urgency, a valid animal model of rash action would provide a foundation upon which these systems can be better studied. If the neurobehavioral causes of urgency are better understood, risk can be reduced in a more effective way, and impulsivity in predisposed individuals may be reduced if drugs can be developed to specifically target these brain areas implicated in urgency. PUBLIC HEALTH RELEVANCE: Impulsivity is known to be a risk factor for various negative health-related behaviors, including drug abuse. This project will assess a behavioral model of impulsivity in both rat and human subjects to determine its usefulness in relation to personality questionnaires that are typically used to assess impulsivity in humans. This work will advance our basic knowledge about the neural mechanisms of impulsive behavior and drug abuse.