Cocaine, Impusivity, and Stratal Function in NHPs

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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.