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

Neuropsychopharmacology volume 47, pages 276–291 (2022)Cite this article

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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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Fig. 1: Disturbances in the drug-addicted brain as described by the iRISA framework.
Fig. 2: The PFC in drug addiction as a function of time.
Fig. 3: The PFC mechanisms of recovery as supported by the iRISA framework.

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Funding

RZG is supported by grants from the National Institute on Drug Abuse (R01DA048301, R01DA041528, R01DA047851, 271201800035C) and the National Center for Complementary and Integrative Health (R01AT010627). CWB is supported by the National Institute on Drug Abuse Intramural Research Program.

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Affiliations

  1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Ahmet O. Ceceli & Rita Z. Goldstein

  2. NIDA Intramural Research Program, Baltimore, MD, USA

    Charles W. Bradberry

  3. Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Rita Z. Goldstein

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  1. Ahmet O. Ceceli
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  2. Charles W. Bradberry
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  3. Rita Z. Goldstein
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AOC, CWB, and RZG wrote the manuscript.

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Correspondence to Rita Z. Goldstein.

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Ceceli, A.O., Bradberry, C.W. & Goldstein, R.Z. The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex. Neuropsychopharmacol. 47, 276–291 (2022). https://doi.org/10.1038/s41386-021-01153-9

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