Cited by 119Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesSubstance Abuse Treatment and Outcomes

The Orbitofrontal Cortex, Impulsivity, and Addiction: Probing Orbitofrontal Dysfunction at the Neural, Neurochemical, and Molecular Level

WINSTANLEY, CATHARINE A.·2007·Annals of the New York Academy of Sciences

Abstract

The association between impulsivity and addiction is currently a topic of intense research interest. Investigations into the neurobiological basis of aspects of impulse control have revealed some striking parallels between the brain circuitry and neurochemical systems implicated in drug dependence and impulsive behavior. Both processes are heavily regulated by limbic corticostriatal circuits including the orbitofrontal cortex (OFC) and nucleus accumbens (NAC), and are modulated by dopamine (DA) and serotonin (5-HT). Hypoactivity within the OFC has been observed in recently abstinent cocaine users, and this is thought to contribute to the cognitive deficits associated with drug abuse, including impairments in impulse control. However, the neurobiological mechanisms underlying these functional and behavioral deficits are unclear. In parallel to observations made in the NAC, recent data indicate that chronic cocaine use also induces the transcription factor DeltaFosB in the OFC and that this plays a role in the cognitive sequelae of chronic cocaine administration. In particular, DeltaFosB appears to be involved in the development of tolerance to the disruptive effects of acute cocaine on impulsivity and motivation observed after repeated cocaine administration. Increased DeltaFosB also contributes to increased impulsivity during withdrawal from the drug. Both effects could be attributed to the up-regulation of local inhibitory processes in the OFC after over-expression of DeltaFosB and chronic cocaine treatment. Through integrating what is known of the interaction between addictive drugs and impulsivity at the neural, neurochemical, and molecular level, novel insight may be obtained into the multi-faceted regulation of the addicted state.

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Crossref · 10.1196/annals.1401.024

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  • Reciprocal connections among frontal cortical regions, hippocampal-amygdala limbic areas, and striatal regions regulate goal-directed behavior.

    “Reciprocal connections between frontal cortical brain regions, hippocampal-amygdala limbic brain areas and striatal regions regulate goal directed behavior (Winstanley, 2007).”

    From Impulsivity, frontal lobes and risk for addiction (2009) · cites this paper as Winstanley, 2007

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Authors
WINSTANLEY, C. A.
Affiliations
University of British Columbia (CA)
Corresponding author
WINSTANLEY, CATHARINE A.
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2007-12
Volume
1121
Issue
1
Pages
639-655
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
OpenAlex
W2044346852
Cited by
119
References
71
Citations by year
2026: 4 · 2025: 6 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 11 · 2013: 12 · 2012: 11
FWCI
3.42
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of the New York Academy of Sciences (publishedVersion)
  • PubMed (publishedVersion)
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
orbitofrontal cortex, impulsivity, addiction, cocaine, ΔFosB, nucleus accumbens, dopamine, serotonin, impulse control, drug addiction, cocaine withdrawal, cognitive impairment, corticostriatal circuits, inhibitory interneurons
MeSH terms
Animals, Pharmaceutical Preparations, Frontal Lobe, Humans, Neurons, Behavior, Addictive, Substance-Related Disorders

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