The addicted human brain viewed in the light of imaging studies brain circuits and treatment strategies.pdfVIP

Neuropharmacology 47 (2004) 3–13 /locate/neuropharm The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies Nora D. Volkow a,b,c,?, Joanna S. Fowler d, Gene-Jack Wang c a O?ce of the Director, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, MSC 9581, Bethesda, MD 20892, USA b National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA c Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA d Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA Received 18 May 2004; received in revised form 12 July 2004; accepted 21 July 2004 Abstract Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the ?ndings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in DA induced by drugs of abuse. We hypothesize that this supraphysiological e?ect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases DA neurotransmission, chronic drug consumption results in a marked decrease in DA activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse a?ect the brain suggests strategies for intervention, which might include: (a) thos