Cue-triggered Reward Seeking

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Addictive urges often have several specific motivation features: the motivational urge is a) highly intense, b) narrowly focused on the addicted target (e.g., drugs), and c) sometimes seemingly `irrational', in the sense of not being explainable by past or expected reinforcement values even for the addicts themselves. For example, relapse can occur even when the addict is no longer in withdrawal, and knows from past experience that the available drug is not very pleasant, and does not expect the future drug to be very pleasant. Here we use optogenetic tools to study brain mechanisms that generate these powerful motivation features. This proposal takes advantage of our recent discovery that optogenetic stimulation of amygdala-related circuitry creates powerful motivational urges for cocaine or sucrose rewards that are a) narrowly focused, b) highly intense, and c) irrational in the sense of exceeding the sum of component reinforcements. This manipulation recreates in the laboratory the same features of motivation that need understanding in addiction. Experiment 1 will identify the crucial anatomical site within amygdala, and identify the particular neuron subpopulations, responsible for generating this intense yet narrow urge for a particular reward, even at the expense of other rewards. Experiment 2 will examine larger brain interactions of the amygdala with mesolimbic circuits, to identify the responsible larger brain circuitry. Experiment 3 will examine how drug-induced mesolimbic sensitization interacts with this circuitry to exacerbate these three features of addictive-like motivation. Altogether, these studies will help clarify how brain mechanisms generate excessive yet narrow, and even irrational, urges (similar to the addictive urges that make drug addicts relapse).