Dopamine in drug abuse and addiction: results from imaging studies and treatment implications

Volkow, N D; Fowler, J S; Wang, G-J; Swanson, J M

doi:10.1038/sj.mp.4001507

Cited by 1,101Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesNeural and Behavioral Psychology Studies

Dopamine in drug abuse and addiction: results from imaging studies and treatment implications

Volkow, N D, Fowler, J S, Wang, G-J, Swanson, J M·2004·Molecular Psychiatry

DOI 10.1038/sj.mp.4001507

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Abstract

The involvement of dopamine in drug reinforcement is well recognized but its role in drug addiction is much less clear. Imaging studies have shown that the reinforcing effects of drugs of abuse in humans are contingent upon large and fast increases in dopamine that mimic but exceed in the intensity and duration those induced by dopamine cell firing to environmental events. In addition, imaging studies have also documented a role of dopamine in motivation, which appears to be encoded both by fast as well as smooth DA increases. Since dopamine cells fire in response to salient stimuli, the supraphysiological activation by drugs is likely to be experienced as highly salient (driving attention, arousal conditioned learning and motivation) and may also reset the thresholds required for environmental events to activate dopamine cells. Indeed, imaging studies have shown that in drug-addicted subjects, dopamine function is markedly disrupted (decreases in dopamine release and in dopamine D2 receptors in striatum) and this is associated with reduced activity of the orbitofrontal cortex (neuroanatomical region involved with salience attribution and motivation and implicated in compulsive behaviors) and the cingulate gyrus (neuroanatomical region involved with inhibitory control and attention and implicated in impulsivity). However, when addicted subjects are exposed to drug-related stimuli, these hypoactive regions become hyperactive in proportion to the expressed desire for the drug. We postulate that decreased dopamine function in addicted subjects results in decreased sensitivity to nondrug-related stimuli (including natural reinforcers) and disrupts frontal inhibition, both of which contribute to compulsive drug intake and impaired inhibitory control. These findings suggest new strategies for pharmacological and behavioral treatments, which focus on enhancing DA function and restoring brain circuits disrupted by chronic drug use to help motivate the addicted subject in activities that provide alternative sources of reinforcement, counteract conditioned responses, enhance their ability to control their drive to take drugs and interfere with their compulsive administration.

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Addictive substances lead to further blunting of the reward response, particularly in the ventral striatum.
“Thus, addictive substances lead to further blunting of the reward response,180 particularly in the VS.”
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Neurocircuitry of Addiction
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Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications
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The Neural Basis of Addiction: A Pathology of Motivation and Choice
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Inhibition and impulsivity: behavioral and neural basis of response control
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Is there a common molecular pathway for addiction?
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Earlier development of the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adolescents.
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Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction
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How can drug addiction help us understand obesity?
Volkow, N. D., & Wise, R. A. (2005) · Nature Neuroscience · doi:10.1038/nn1452 · Cited by 1,089 · see citing works
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Regulation of firing of dopaminergic neurons and control of goal-directed behaviors
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Imaging dopamine's role in drug abuse and addiction
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Widespread reward-system activation in obese women in response to pictures of high-calorie foods
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Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology
Volkow, N. D., Wang, G.-J., Fowler, J. S., & Telang, F. (2008) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2008.0107 · Cited by 809 · see citing works
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Placebo Effects Mediated by Endogenous Opioid Activity on μ-Opioid Receptors
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Neural correlates of food addiction
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Early-Life Adversity and Physical and Emotional Health Across the Lifespan: A Neuroimmune Network Hypothesis
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Drug addiction: the neurobiology of disrupted self-control
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Dopamine in Drug Abuse and Addiction: Results of Imaging Studies and Treatment Implications
Volkow, N. D., Fowler, J. S., Wang, G.-J., Swanson, J. M., & Telang, F. (2007) · Archives of Neurology · doi:10.1001/archneur.64.11.1575 · Cited by 605 · see citing works
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Excessive discounting of delayed reinforcers as a trans-disease process contributing to addiction and other disease-related vulnerabilities: Emerging evidence
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Biological substrates of reward and aversion: A nucleus accumbens activity hypothesis
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Obese women show greater delay discounting than healthy-weight women
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Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders
Seo, D., Patrick, C. J., & Kennealy, P. J. (2008) · Aggression and Violent Behavior · doi:10.1016/j.avb.2008.06.003 · Cited by 520 · see citing works
Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study
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The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives
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Internet and Gaming Addiction: A Systematic Literature Review of Neuroimaging Studies
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Ventral–striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analytic review of the fMRI literature
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Dopaminergic mechanisms of individual differences in human effort-based decision-making
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Childhood Adversity Is Associated with Left Basal Ganglia Dysfunction During Reward Anticipation in Adulthood
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Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking
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Long-acting medications for the hyperkinetic disorders: A systematic review and European treatment guideline
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Internet addiction in adolescence: neurobiological, psychosocial and clinical issues
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Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride
Frank, G. K., Bailer, U. F., Henry, S. E., Drevets, W., Meltzer, C. C., Price, J. C., Mathis, C. A., Wagner, A., Hoge, J., Ziolko, S., et al. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.05.003 · Cited by 361 · see citing works
Dopaminergic dynamics underlying sex-specific cocaine reward
Calipari, E. S., Juarez, B., Morel, C., Walker, D. M., Cahill, M. E., Ribeiro, E., Roman-Ortiz, C., Ramakrishnan, C., Deisseroth, K., Han, M.-H., et al. (2017) · Nature Communications · doi:10.1038/ncomms13877 · Cited by 359 · see citing works
Natural rewards, neuroplasticity, and non-drug addictions
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Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis
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Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.
Han, D. H., Hwang, J. W., & Renshaw, P. F. (2010) · Experimental and Clinical Psychopharmacology · doi:10.1037/a0020023 · Cited by 324 · see citing works
Modeling stress and drug craving in the laboratory: implications for addiction treatment development
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Authors: Volkow, N. D., Fowler, J. S., Wang, G.-J., & Swanson, J. M.
Affiliations: National Institute on Drug Abuse (US)
Brookhaven National Laboratory (US)
University of California, Irvine (US)
Corresponding author: Volkow, N D
ORCID: Volkow, N D
Swanson, J M
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2004-04-06
Volume: 9
Issue: 6
Pages: 557-569
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/sj.mp.4001507
OpenAlex: W1980277133
Cited by: 1,101
References: 131
Citations by year: 2026: 22 · 2025: 32 · 2024: 20 · 2023: 37 · 2022: 34 · 2021: 40 · 2020: 87 · 2019: 39 · 2018: 43 · 2017: 39 · 2016: 69 · 2015: 71 · 2014: 78 · 2013: 55 · 2012: 60
FWCI: 3.62
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: Office of National Drug Control Policy
National Institutes of Health (5r01da009490-08)
National Institute on Alcohol Abuse and Alcoholism (AA-09481, R01AA009481)
National Institute on Drug Abuse (DA-06891, DA-09490, DA-06278, R01DA006278, R01DA006891)
Biological and Environmental Research
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: dopamine, drug addiction, drug reinforcement, motivation, salience, orbitofrontal cortex, cingulate gyrus, dopamine D2 receptor, striatum, impulsivity, inhibitory control, pharmacotherapy, behavior therapy
MeSH terms: Attention Deficit Disorder with Hyperactivity, Brain, Child, Dopamine, Humans, Neurons, Substance-Related Disorders

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Dopamine in drug abuse and addiction: results from imaging studies and treatment implications

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