The purpose of this Review is twofold. First, we aim to elaborate a heuristic framework based on the neuropsychopharmacological and brain imaging phenotype of addiction in the context of three functional domains (incentive salience, negative emotional states, and executive function) mediated by three major neuro-biological circuits (basal ganglia, extended amygdala, and prefrontal cortex). Second, we aim to identify neurochemically defined mini circuits that can independently or interactively mediate functional neuroplasticity within the three major circuits to produce incentive salience and compulsive-like habits, negative emotional states of low reward and excessive stress, and compromised executive function. Building on previous identification of the three overall domains, this Review provides a framework for integration of the ever-expanding neuroplastic complexity of motivational systems that are involved in addiction and for identification of new targets for diagnosis, treatment, and prevention of addiction.
