Neuropsychopharmacology Reviews

Neurocircuitry of Addiction

  • Neuropsychopharmacology 35, 217238 (2010)
  • doi:10.1038/npp.2009.110
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Abstract

Drug addiction is a chronically relapsing disorder that has 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. 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 key role 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 these structures 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 the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.

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Acknowledgements

This is publication number 20084 from The Scripps Research Institute. Preparation of this work was supported by the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grants AA12602, AA08459, and AA06420 from the National Institute on Alcohol Abuse and Alcoholism; DA04043, DA04398, and DA10072 from the National Institute on Drug Abuse; DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases; and 17RT-0095 from the Tobacco-Related Disease Research Program from the State of California. We thank Michael Arends and Ruben Baler for their assistance with paper preparation.

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  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA

    • George F Koob
  2. National Institute on Drug Abuse, Bethesda, MD, USA

    • Nora D Volkow

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Correspondence to George F Koob.

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The authors declare no conflicts of interest.