Cited by 640Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchSubstance Abuse Treatment and Outcomes

ΔFosB: A sustained molecular switch for addiction

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Nestler, Eric J., Barrot, Michel, Self, David W.·2001·Proceedings of the National Academy of Sciences

Abstract

The longevity of some of the behavioral abnormalities that characterize drug addiction has suggested that regulation of neural gene expression may be involved in the process by which drugs of abuse cause a state of addiction. Increasing evidence suggests that the transcription factor ΔFosB represents one mechanism by which drugs of abuse produce relatively stable changes in the brain that contribute to the addiction phenotype. ΔFosB, a member of the Fos family of transcription factors, accumulates within a subset of neurons of the nucleus accumbens and dorsal striatum (brain regions important for addiction) after repeated administration of many kinds of drugs of abuse. Similar accumulation of ΔFosB occurs after compulsive running, which suggests that ΔFosB may accumulate in response to many types of compulsive behaviors. Importantly, ΔFosB persists in neurons for relatively long periods of time because of its extraordinary stability. Therefore, ΔFosB represents a molecular mechanism that could initiate and then sustain changes in gene expression that persist long after drug exposure ceases. Studies in inducible transgenic mice that overexpress either ΔFosB or a dominant negative inhibitor of the protein provide direct evidence that ΔFosB causes increased sensitivity to the behavioral effects of drugs of abuse and, possibly, increased drug seeking behavior. This work supports the view that ΔFosB functions as a type of sustained “molecular switch” that gradually converts acute drug responses into relatively stable adaptations that contribute to the long-term neural and behavioral plasticity that underlies addiction.

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  1. [31]Yen, J., Wisdom, R. M., Tratner, I. & Verma, I. M. (1991) Proc. Natl. Acad. Sci. USA 88, 5077-5081.
  2. [42]Carey, M. & Smale, S. T. (2000) Transcriptional Regulation in Eukaryotes (Cold Spring Harbor Lab. Press, Plainview, NY).

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Authors
Nestler, E. J., Barrot, M., & Self, D. W.
Affiliations
The University of Texas Southwestern Medical Center (US)
Venue
Proceedings of the National Academy of Sciences
Published
2001-09-25
Volume
98
Issue
20
Pages
11042-11046
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2000696407
Cited by
640
References
45
Citations by year
2026: 24 · 2025: 32 · 2024: 41 · 2023: 31 · 2022: 27 · 2021: 30 · 2020: 17 · 2019: 25 · 2018: 23 · 2017: 23 · 2016: 24 · 2015: 22 · 2014: 17 · 2013: 29 · 2012: 27
FWCI
1.91
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
ΔFosB, drug addiction, transcription factors, Fos family, nucleus accumbens, dorsal striatum, drug-seeking behavior, neuronal gene expression, behavioral plasticity, transgenic mice, protein stability
MeSH terms
Animals, Brain, Humans, Models, Neurological, Neurons, Proto-Oncogene Proteins c-fos, Genes, fos, Substance-Related Disorders

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