Drug addiction

REVIEW

Neuropsychopharmacology REVIEWS (2010) 35, 217–238

& 2010 Nature Publishing Group All rights reserved 0893-133X/10 $32.00 ...............................................................................................................................................................
www.neuropsychopharmacology.org

217

Neurocircuitry of Addiction                                                 George F Koob*,1 and Nora D Volkow2
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA; 2National Institute on Drug Abuse, Bethesda, MD, USA
1

Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) lossof control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages:‘binge/intoxication’, ‘withdrawal/negative affect’, and ‘preoccupation/anticipation’ (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a keyrole in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex–dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of thesestructures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for themolecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction. Neuropsychopharmacology Reviews (2010) 35, 217–238; doi:10.1038/npp.2009.110; published online 26 August 2009

CONCEPTUAL FRAMEWORK
Addiction Definitions: Drug Use, Abuse, and Dependence Addiction Cycle
Drug addiction is a chronically relapsing disorder thathas been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented (defined as Substance Dependence by the Diagnostic and Statistical Manual of Mental Disorders [DSM] of the AmericanPsychiatric Association; Koob and Le Moal, 1997; Table 1). The occasional but limited use of an abusable drug is clinically distinct from escalated drug use, loss of control over limiting drug intake, and the emergence of chronic compulsive drug-seeking that characterizes addiction. The
*Correspondence: Dr GF Koob, Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute,10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, USA, Tel: + 1 858 784 7062, Fax: + 1 858 784 7405, E-mail: gkoob@scripps.edu Received 28 March 2009; revised 13 July 2009; accepted 14 July 2009

critical nature of the distinction between drug use, abuse, and dependence has been illuminated by data showing that approximately 15.6% (29 million) of the US adult population will go on...