Prefrontal cortex and drug abuse vulnerability: Translation to prevention and treatment interventions
Open accessAbstract
Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals.
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Pre-existing prefrontal cortex dysfunction due to genetic factors, head trauma, or neurodevelopmental insults is recognized as a vulnerability risk factor for SUDs.
“Pre- existing prefrontal cortex dysfunction due to genetic fac tors, head trauma, or neurodevelopmental insults is recognized as a vulnerability risk factor for SUDs 60 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [60]
The Prevention section (5.1; page not provided) links pre-existing PFC dysfunction to increased drug-abuse risk through ADHD. The Developmental Differences section (4.1; page not provided) also discusses developmental influences on PFC function and vulnerability. The passages do not establish genetic factors, head trauma, or neurodevelopmental insults as the specific causes of the dysfunction described in the claim. (LLM, conf=0.86)
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- Authors
- Perry, J. L., Joseph, J. E., Jiang, Y., Zimmerman, R. S., Kelly, T. H., Darna, M., Huettl, P., Dwoskin, L. P., & Bardo, M. T.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Bardo, Michael T.
- Venue
- Brain Research Reviews
- Publisher
- Elsevier BV
- Published
- 2011-01-01
- Volume
- 65
- Issue
- 2
- Pages
- 124-149
- ISSN
- 0165-0173 (ISSN-L)
- PMC
- PMC3005953
- OpenAlex
- W1969360450
- Cited by
- 180
- References
- 366
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 12 · 2016: 11 · 2015: 25 · 2014: 18 · 2013: 16 · 2012: 14
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA012964, T32DA007304, P50DA005312, P50 DA05312, R21DA024401)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- prefrontal cortex, drug abuse vulnerability, reward processing, impulsivity, medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, monoamines, amino acid neurotransmitters, behavioral inhibition, decision-making, individual differences, age and sex differences, substance use prevention, addiction treatment, transcranial direct current stimulation, cognitive exercises, physical activity, pharmacotherapy, public service announcements
- MeSH terms
- Animals, Exploratory Behavior, Humans, Impulsive Behavior, Motivation, Reward, Risk Factors, Prefrontal Cortex, Substance-Related Disorders, Genetic Predisposition to Disease, Risk Reduction Behavior, Rats, Executive Function
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