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      Neurobiology of addiction: a neurocircuitry analysis

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      The lancet. Psychiatry

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          Abstract

          Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.

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          Author and article information

          Journal
          101638123
          42935
          Lancet Psychiatry
          Lancet Psychiatry
          The lancet. Psychiatry
          2215-0366
          2215-0374
          17 August 2018
          August 2016
          12 September 2018
          : 3
          : 8
          : 760-773
          Affiliations
          National Institute on Alcohol Abuse and Alcoholism (G F Koob PhD) and National Institute on Drug Abuse (N D Volkow MD), National Institutes of Health, Rockville, MD, USA
          Author notes

          Contributors

          Both authors contributed equally to writing the manuscript.

          Correspondence to: Dr George F Koob, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2001, Suite 2000, Rockville, MD 20852, USA gkoob@ 123456scripps.edu
          Article
          PMC6135092 PMC6135092 6135092 nihpa985499
          10.1016/S2215-0366(16)00104-8
          6135092
          27475769
          7cd7425e-00cc-44a6-8788-407dfa7cf702
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