Recovering drug addicts encounter danger when faced with drug-related cues or contexts, because those situations can trigger relapse. Similarly, bouts of binge eating are often triggered by cues for food relevant rewards. Cues are especially potent triggers when individuals are in vulnerable states. These proposal aims to identify the brain states that cause vulnerability to cue-triggered 'wanting'of reward. The responsible brain mechanisms particularly involve the limbic nucleus accumbens and amygdala. Here we will study how these brain mechanisms cause excessive incentive salience ('wanting') to be attributed to particular reward cues. In experiment 1, microinjections of agonist drugs and a Fos plume mapping tool will be used to identify the neural mechanisms in nucleus accumbens and amygdala that magnify cue-triggered 'wanting'. In experiment 2, the circuit principles that join together the nucleus accumbens and amygdala into a cooperative system will be identified by manipulating the structures with multiple simultaneous microinjections. In experiment 3, prior neural sensitization and learning manipulations will help show how natural 'wanting'mechanisms are usurped by drugs and sensitization to cause an addicted reward to be 'wanted'more than other rewards. These studies will help clarify the brain and psychological mechanisms that cause addicts to excessively 'want'drug and binge eaters to excessively 'want'food rewards. PUBLIC HEALTH RELEVANCE: A primary problem in drug addiction and binge eating disorders is the continuing danger for relapse posed by encounters with cues for the addicted reward (even after long periods of abstinence). A brain mechanism has been hypothesized to cause cue-triggered relapse, namely incentive sensitization of brain systems that generate normal 'wanting'for rewards. The studies proposed here will help reveal those brain mechanisms underlying cue-triggered relapse, and will shed light on how compulsive 'wants'are produced in addiction and in eating disorders.