Repeated cocaine exposure and striatal contributions to cognitive control

描述（由申请人提供）：成瘾会逐渐改变大脑，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，即调节自己的思想、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是如何损害认知控制的。我们将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，通过测量单个神经元的动作电位，同时需要服用和不服用可卡因。我们使用猴子的主要原因是，它们的心理与认知控制相似，与人类不同的是，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卡片分类任务的一个版本。在每次试验中，猴子从三种颜色的形状中选择一种；他们必须遵守的正确选择的规则经常随机变化。人类和猴子在这项任务中的表现是认知控制的一个很好的衡量标准，并将使我们了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。我们将记录纹状体的三个亚区域的活动，纹状体是药物滥用的主要目标，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服用可卡因，然后确定反复接触可卡因是如何改变认知控制行为和神经活动的。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它的影响提供一个基本的理解。

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.