Repeated cocaine exposure and striatal contributions to cognitive control

反复接触可卡因和纹状体对认知控制的贡献

基本信息

批准号：
9270009
负责人：
BENJAMIN Y HAYDEN
金额：
$ 13.98万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9270009
关键词：
Action Potentials Affect American Anatomy Animals Attention Behavior Behavior Control Behavioral Brain Brain region Chronic Cocaine Cognition Color Complex Corpus striatum structure Decision Making Diagnosis Disease Drug Targeting Drug usage Electrodes Elements Failure Future Goals Habits Human Impaired cognition Intervention Laboratories Lead Macaca mulatta Maintenance Measures Mediating Monkeys National Institute of Drug Abuse Neurons Performance Pharmaceutical Preparations Play Psychologist Psychology Research Rewards Rodent Role Schedule Self-Administered Services Shapes Signal Transduction Sorting - Cell Movement Stimulus Testing Thinking Training Variant Ventral Striatum Wisconsin Work addiction base caudate nucleus cocaine exposure cognitive change cognitive control cost drug abuse prevention drug of abuse drug seeking behavior flexibility goal oriented behavior improved interest non-drug novel outcome prediction public health relevance putamen relating to nervous system response

项目摘要

DESCRIPTION (provided by applicant): Addiction gradually changes the brain and reduces the addicts' ability to behave in accordance with long-term goals. Healthy goal-oriented behavior requires what psychologists call cognitive control, the ability to regulate one's own thoughts, plans, and actions. The major research goal of this project is to understand how cocaine impairs cognitive control. We will study brain activity in the most direct way possible: by measuring action potentials from single neurons while monkeys perform a task that requires cognitive control both on and off cocaine. The main reason we will use monkeys is that their psychology as it relates to cognitive control is similar to that of humans and, unlike humans, we can easily measure responses of their neurons. Our monkeys will perform a version of the well-known Wisconsin Card Sorting Task. On each trial monkeys select one of three colored shapes; the rule they must obey to choose correctly changes frequently and randomly. Performance on this task in humans and monkeys is a good measure of cognitive control and will allow us to understand three specific elements of cognitive control: associative encoding, rule maintenance, and switch signaling. We will record activity in three subregions of the striatum, a brain region that is a major target for drugs of abuse and is likely to be a significant player in cognitive control. Once we have a basic understanding of the role of striatum in cognitive control, we will train the monkeys to self-administer cocaine and then determine how repeated exposure to cocaine changes cognitive control behavior and neural activity. Successful completion of this work will provide a fundamental understanding of the neural basis of the striatum's role in cognitive control and the effects of cocaine on it.

描述（由申请人提供）：成瘾会逐渐改变大脑并降低成瘾者按照长期目标行事的能力。以目标为导向的健康行为需要心理学家所说的认知控制，即调节自己的想法、计划和行动的能力。该项目的主要研究目标是了解可卡因如何损害认知控制。我们将以最直接的方式研究大脑活动：通过测量单个神经元的动作电位，同时猴子执行需要在使用和不使用可卡因的情况下进行认知控制的任务。我们使用猴子的主要原因是，它们与认知控制相关的心理与人类相似，并且与人类不同的是，我们可以轻松测量它们神经元的反应。我们的猴子将执行著名的威斯康星州卡片分类任务的一个版本。在每次试验中，猴子选择三种颜色形状中的一种；他们为了正确选择而必须遵守的规则经常和随机地变化。人类和猴子在这项任务上的表现是认知控制的一个很好的衡量标准，将使我们能够理解认知控制的三个特定要素：联想编码、规则维护和转换信号。我们将记录纹状体三个分区的活动，该大脑区域是滥用药物的主要目标，并且可能在认知控制中发挥重要作用。一旦我们对纹状体在认知控制中的作用有了基本的了解，我们将训练猴子自我施用可卡因，然后确定重复接触可卡因如何改变认知控制行为和神经活动。这项工作的成功完成将为纹状体在认知控制中的作用的神经基础以及可卡因对其的影响提供一个基本的了解。