Cocaine, Impusivity, and Stratal Function in NHPs

NHP 中的可卡因、冲动性和层层功能

• 批准号: 7797227
• 负责人: DAEYEOL LEE
• 金额: $ 16.75万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797227
• 关键词: Accounting; Addictive Behavior; Affect; Anatomy; Animals; Area; Artificial Intelligence; Basal Ganglia; Behavior; Behavior Control; Behavioral; Brain; Characteristics; Cocaine; Complex; Corpus striatum structure; Data; Decision Making; Dorsal; Drug Addiction; Drug abuse; Economics; Eye Movements; Failure; Frequencies; Goals; Impairment; Impulsive Behavior; Impulsivity; Individual; Intervention; Knowledge; Lead; Life; Measures; Mediating; Mental disorders; Monkeys; Motor; Movement; Nature; Neurons; Neurosciences; Neurosciences Research; Peripheral; Pharmaceutical Preparations; Physiology; Play; Prefrontal Cortex; Preparation; Primates; Process; Psychology; Reaction; Rewards; Role; Running; Sensory; Shapes; Signal Transduction; Societies; Speed; Substance abuse problem; Testing; Time; Training; Translational Research; Ventral Striatum; Wit; addiction; caudate nucleus; cocaine exposure; design; discount; drug abuser; drug addict; functional disability; neural patterning; neuroimaging; neuromechanism; preference; relating to nervous system; research study; response

Drug addiction can be characterized by the impaired abilities to choose the course of action that is likely to lead to the best long-term consequences for the affected individual and society. In particular, two different forms of impulsivity might both contribute to the initiation of addictive behaviors and become exacerbated by them. First, compared to healthy controls, drug addicts tend to show stronger preference for an immediate reward over a more delayed but larger reward. This is referred to as choice impulsivity. Second, drug abusers tend to initiate actions prematurely before the sufficient evidence for such actions is accumulated. This is referred to as response impulsivity. A main goal of Project 3 is to invesfigate how these two types of impulsivity might be mediated by the striatum in primates, and to test whether cocaine-induced changes in striatal functions might account for changes in the impulsive choices and responses. To investigate choice impulsivity, animals will be trained to perform an inter-temporal choice in which they will choose between two different rewards that differ in their magnitude and immediacy. Their choice impulsivity will be estimated from the steepness of a discount function that describes how the subjective value of reward decreases with the reward delay. Response impulsivity will be measured with a stop-signal task in which the animal receives an instrucfion to produce an eye movement towards a peripheral target in every trial but is also required to cancel such movement when a second "stop" signal is presented. The time necessary to cancel the unwanted movement will be estimated to quantify response impulsivity. We will then characterize and compare the activity of individual neurons in the caudate nucleus and ventral striatum while the animals perform each of these two tasks before and after cocaine exposure. Specifically, we will test whether the striatal acfivity related to the reward magnitude and delay will be differenfially affected by cocaine exposure. We will also test whether the striatal activity related to the preparation and cancellation of visually guided eye movements are modified by cocaine. The results from these experiments will elucidate the role of striatum in drug addiction.

吸毒成瘾的特征是选择行动路线的能力受损，这很可能是 为受影响的个人和社会带来最好的长期后果。特别是，两种不同的 冲动的形式可能既有助于成瘾行为的开始，也可能因以下原因而加剧 他们。首先，与健康对照相比，吸毒者倾向于表现出更强烈的即刻偏好 奖励比延迟时间更长但更大的奖励。这被称为选择冲动。第二，毒品 施虐者倾向于在积累足够的证据之前过早地采取行动。 这被称为反应冲动。项目3的一个主要目标是研究这两种类型的 灵长类动物的冲动可能是由纹状体介导的，并测试可卡因是否会导致大脑中 纹状体功能可能解释了冲动选择和反应的变化。调查选择 冲动，动物将被训练进行跨期选择，在这两种选择中，它们将在 不同的奖励，在大小和即时性上有所不同。他们的选择冲动将被估计 从一个贴现函数的陡度来看，它描述了奖励的主观价值是如何随着 悬赏延迟。反应冲动性将通过停止信号任务来测量，在该任务中，动物 在每次试验中都会收到指示，以产生朝向外围目标的眼球运动，但也 当出现第二个“停止”信号时，需要取消这种移动。取消所需的时间 不想要的移动将被估计为量化的反应冲动。然后我们将描述和描述 比较动物尾状核和腹侧纹状体单个神经元的活动 在接触可卡因之前和之后分别执行这两项任务。具体地说，我们将测试 纹状体活性与奖赏大小和延迟有关，受可卡因暴露的影响不同。 我们还将测试纹状体活动是否与视觉引导眼的准备和取消有关 可卡因会改变人的动作。这些实验的结果将阐明纹状体在 吸毒成瘾。