Repeated cocaine exposure and striatal contributions to cognitive control

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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.