Repeated cocaine exposure and striatal contributions to cognitive control

描述(由申请者提供)：成瘾逐渐改变大脑，降低成瘾者按照长期目标行事的能力。健康的目标导向行为需要心理学家所说的认知控制，即控制自己的想法、计划和行动的能力。这个项目的主要研究目标是了解可卡因如何损害认知控制。我们将尽可能以最直接的方式研究大脑活动：在猴子执行一项需要认知控制的任务时，测量单个神经元的动作电位，无论是服用可卡因还是戒除可卡因。我们将使用猴子的主要原因是，它们与认知控制有关的心理与人类相似，而且与人类不同，我们可以很容易地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。在每一次实验中，猴子从三种颜色的形状中选择一种；它们必须遵守的规则才能正确地选择，变化频繁且随机。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元素：联想编码、规则维护和开关信号。我们将记录纹状体三个亚区的活动，这是一个大脑区域，是滥用药物的主要目标，很可能是认知控制的重要参与者。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注射可卡因，然后确定反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提供对纹状体在认知控制中作用的神经基础以及可卡因对其影响的基本了解。

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.