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

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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

DOI 10.1073/pnas.191352698PMC PMC58680

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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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Autoradiographic localization of dopamine D1 and D2 receptors in rat nucleus accumbens: Resistance to differential rearing conditions
Bardo, M. T., & Hammer, R. P. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90226-e · Cited by 3,229
Molecular basis of long-term plasticity underlying addiction
Nestler, E. J. (2001) · Nature reviews. Neuroscience · doi:10.1038/35053570 · Cited by 1,893
Self-citation
Addiction, Dopamine, and the Molecular Mechanisms of Memory
Berke, J. D., & Hyman, S. E. (2000) · Neuron · doi:10.1016/s0896-6273(00)81056-9 · Cited by 1,184
Neuroscience of addiction
Koob, G. F., Sanna, P. P., & Bloom, F. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)80557-7 · Cited by 1,026
Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum.
Graybiel, A. M., Moratalla, R., & Robertson, H. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.17.6912 · Cited by 957
Regulation of cocaine reward by CREB
Carlezon, W. A., Thome, J., Olson, V. G., Lane-Ladd, S. B., Brodkin, E. S., Hiroi, N., Duman, R. S., Neve, R. L., & Nestler, E. J. (1998) · Science · doi:10.1126/science.282.5397.2272 · Cited by 767
Self-citation
Beyond the Dopamine Receptor
Greengard, P., Allen, P. B., & Nairn, A. C. (1999) · Neuron · doi:10.1016/s0896-6273(00)80798-9 · Cited by 761
Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine
Robinson, T. E., & Kolb, B. E. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00576.x · Cited by 726
Drug-activation of brain reward pathways
Wise, R. A. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00063-5 · Cited by 684
Synaptic plasticity and dynamic modulation of the postsynaptic membrane
Lüscher, C., Nicoll, R. A., Malenka, R. C., & Müller, D. (2000) · Nature Neuroscience · doi:10.1038/75714 · Cited by 662

Show all 45 references

Research works printed but not linked: 5

H Nye, B T Hope, M Kelz, M Iadarola, E J Nestler J Pharmacol Exp Ther 275, 1671–1680 (1995).
H E Nye, E J Nestler Mol Pharmacol 49, 636–645 (1996).
J S Chen, H E Nye, M B Kelz, N Hiroi, Y Nakabeppu, B T Hope, E J Nestler Mol Pharmacol 48, 880–889 (1995).
F J White, X-T Hu, X-F Zhang, M E Wolf J Pharmacol Exp Ther 273, 445–454 (1995).
M Carey, S T Smale Transcriptional Regulation in Eukaryotes (Cold Spring Harbor Lab. Press, Plainview, NY, 2000).

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“The 35–37 kD isoforms of ΔFosB play a significant role in the brain’s response to chronic drug exposure [76].”
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“Due to its long protein half-life, the psychostimulant-induced AP-1 family member D FOSB (encoded by the Fosb gene) may be in a unique position to serve as a “molecular switch” facilitating the stabilization of activity-dependent epigenetic modiﬁcations across the genome [67].”
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Self-citation
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“In a recent study, however, ΔFosB, a transcription factor involved in drug-induced neuroplasticity (Nestler et al ., 2001), was found to be elevated in the reward-related brain regions following oral oxycodone consumption (Iyer et al ., 2022), similar to parenteral opioid administration studies…”
Result
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Post-weaning social isolation increases the incentive value of nicotine-related contexts and decreases the accumulation of ΔFosB in nucleus accumbens in adolescent rats
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“Taking these findings into account, overexpression of ΔFosB was initially associated with a phenotype of increased drug-seeking and susceptibility to addiction (Nestler, 2008; Nestler et al., 2001).”
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FosB/ΔFosB activation in mast cells regulates gene expression to modulate allergic inflammation in male micePreprint
Duque‐Wilckens, N., Joseph, D., Syed, M., Smith, B., Maradiaga, N. C., Yeh, S.-Y., Srinivasan, V., Sotomayor, F., Durga, K., Nestler, E. J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.06.592755 · Cited by 4
Self-citation
Cocaine-Induced Gene Regulation in D1 and D2 Neuronal Ensembles of the Nucleus Accumbens Revealed by Single-Cell RNA SequencingPreprint
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“Similarly, neuronal activity rapidly induces Fosb , and its Δ Fosb isoform in particular accumulates with repeated cocaine exposure and is crucial for long-term neural and behavioral adaptations associated with addiction 18,35 .”
BackgroundSelf-citation
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Chronic intermittent hypoxia and ovariectomy exert independent and region-specific effects on ΔFosB expression and increase blood pressure in female rats
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Repeated neonatal isoflurane exposure facilitated stress-related fear extinction impairment in male mice and was associated with ΔFosB accumulation in the basolateral amygdala and the hippocampal dentate gyrus
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“FosB and ΔFosB are transcription factors associated with sensibil-ization and addiction to psychostimulant drugs and increase their expression in the addicted state through a mechanism mediated by the D1 receptor [89, 90].”
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Koebele, S. V., Bernaud, V. E., Northup-Smith, S. N., Willeman, M. N., Strouse, I. M., Bulen, H. L., Schrier, A. R., Newbern, J. M., DeNardo, D. F., Mayer, L. P., et al. (2023) · Hormones and Behavior · doi:10.1016/j.yhbeh.2023.105411 · Cited by 3
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“Its long half-life allows it to accumulate in active cells for 1 – 2 weeks (Nestler et al., 2001; McClung et al., 2004).”
Background
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Urrutia-Piñones, J., Illanes-González, J., López-Aguilera, A., Julio‐Pieper, M., & Bravo, J. A. (2018) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-018-0161-x · Cited by 3
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Neurobiological theories of addiction
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Authors: Nestler, E. J., Barrot, M., & Self, D. W.
Affiliations: The University of Texas Southwestern Medical Center (US)
ORCID: Nestler, Eric J.
Barrot, Michel
Self, David W.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2001-09-25
Volume: 98
Issue: 20
Pages: 11042-11046
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.191352698
PMC: PMC58680
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: green
europepmc.org
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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ΔFosB: A sustained molecular switch for addiction

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