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Cited by 150Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesSubstance Abuse Treatment and Outcomes

The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex

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Ceceli, Ahmet O., Bradberry, Charles W., Goldstein, Rita Z.·2022·Neuropsychopharmacology
DOI 10.1038/s41386-021-01153-9PMC PMC8617203
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Abstract

A growing preclinical and clinical body of work on the effects of chronic drug use and drug addiction has extended the scope of inquiry from the putative reward-related subcortical mechanisms to higher-order executive functions as regulated by the prefrontal cortex. Here we review the neuroimaging evidence in humans and non-human primates to demonstrate the involvement of the prefrontal cortex in emotional, cognitive, and behavioral alterations in drug addiction, with particular attention to the impaired response inhibition and salience attribution (iRISA) framework. In support of iRISA, functional and structural neuroimaging studies document a role for the prefrontal cortex in assigning excessive salience to drug over non-drug-related processes with concomitant lapses in self-control, and deficits in reward-related decision-making and insight into illness. Importantly, converging insights from human and non-human primate studies suggest a causal relationship between drug addiction and prefrontal insult, indicating that chronic drug use causes the prefrontal cortex damage that underlies iRISA while changes with abstinence and recovery with treatment suggest plasticity of these same brain regions and functions. We further dissect the overlapping and distinct characteristics of drug classes, potential biomarkers that inform vulnerability and resilience, and advancements in cutting-edge psychological and neuromodulatory treatment strategies, providing a comprehensive landscape of the human and non-human primate drug addiction literature as it relates to the prefrontal cortex.

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  • Connectivity between the prefrontal cortex and striatal regions has been consistently shown to be disrupted in individuals with SUDs.

    “The connectivity between the prefrontal cortex and striatal regions has been consistently shown to be disrupted in individuals with SUDs 59,63,64 .”

    From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [59]

    The Non-drug context section reports reduced white-matter integrity in pathways from the nucleus accumbens to the PFC in tobacco addiction, and the Conclusions section describes striatum–OFC hypoconnectivity as a predictor of addiction vulnerability. These support altered prefrontal–striatal connectivity in specific contexts, but do not establish that it is consistently disrupted across individuals with SUDs. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • In humans with SUD, loss of striatal D2 receptors is associated with impaired activity of the prefrontal cortex.

    “In humans with SUD, the loss of striatal D2 receptors is associated with impaired activity of the prefrontal cortex 58,59 .”

    From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [59]

    The Function and Conclusions sections report impaired prefrontal activity in people with drug addiction. But the passages do not link that impairment to a loss of striatal D2 receptors; searches for D2 receptors and striatal receptor availability found no such association in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Neurobiological similarities between substance addiction and compulsive social media usage are striking, particularly PFC dysfunction critical for impulse control and decision-making.

    “The neurobiological similarities between substance addiction and compulsive social media usage are striking, particularly in terms of prefrontal cortex (PFC) dysfunction, which is critical for impulse control and decision-making [32, 33].”

    From The Impact of Social Media & Technology on Child and Adolescent Mental Health (2025) · cites this paper as [33]

    The Conclusions section links PFC dysfunction in drug addiction to deficits in inhibitory control and reward-related decision-making. Our copy does not establish a neurobiological similarity with compulsive social media use; searches for social media and behavioral addiction did not find a passage addressing that comparison. (LLM, conf=0.86)

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Authors
Ceceli, A. O., Bradberry, C. W., & Goldstein, R. Z.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • National Institute on Drug Abuse (US)
Corresponding author
Goldstein, Rita Z.
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2021-08-18
Volume
47
Issue
1
Pages
276-291
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-021-01153-9
PMC
PMC8617203
OpenAlex
W3194450287
Cited by
150
References
290
Citations by year
2026: 29 · 2025: 31 · 2024: 45 · 2023: 17 · 2022: 25 · 2021: 3
FWCI
3.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (R01DA048301, R01DA041528, 01DA047851, 271201800035C)
  • Intramural Research Program
  • U.S. Department of Health & Human Services | NIH | National Center for Complementary and Integrative Health (R01AT010627)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
drug addiction, prefrontal cortex, response inhibition, salience attribution, self-control, insight into illness, chronic drug use, abstinence, recovery, neuroplasticity, non-human primates, executive function
MeSH terms
Animals, Brain, Prefrontal Cortex, Substance-Related Disorders, Executive Function, Neuroimaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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