The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies
Abstract
Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings 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 effect 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 affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain DA system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets.
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Psychoactive substances can usurp natural reward processing by acting on the mesolimbic dopamine system to drive addictive behavior.
“the processing of natural rewards may be usurped by psychoactive substances that capitalize on the mesolimbic dopamine system to drive addictive behavior.11”
Hedonic dysregulation underlies addiction, stress, and chronic pain, as shown by a shift in the relative salience of natural reward to drug reward in people with severe substance use disorders.
“Though valuation processes are fundamental to survival of the human species, hedonic dysregulation is at the root of an array of clinical disorders, including addiction, stress, and chronic pain, as evidenced by the allostatic shift in the relative salience of natural reward to drug reward observed among persons with severe substance use disorders.”
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- Authors
- Volkow, N. D., Fowler, J. S., & Wang, G.-J.
- Affiliations
- National Institute on Drug Abuse (US)
- Brookhaven National Laboratory (US)
- Corresponding author
- Volkow, Nora D.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 47
- Pages
- 3-13
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2098288561
- Cited by
- 616
- References
- 10
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 6 · 2023: 12 · 2022: 20 · 2021: 14 · 2020: 36 · 2019: 14 · 2018: 23 · 2017: 26 · 2016: 22 · 2015: 32 · 2014: 42 · 2013: 46 · 2012: 46
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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
- drug addiction, dopamine, brain circuits, salience attribution, reward, motivation, inhibitory control, orbitofrontal cortex, cingulate gyrus, compulsive drug taking, addiction treatment, executive function
- MeSH terms
- Brain, Humans, Magnetic Resonance Imaging, Receptors, Drug, Illicit Drugs, Substance-Related Disorders
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