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ΔFosB: A sustained molecular switch for addiction
Open accessAbstract
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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“ΔFOSB is a pivotal transcription factor involved in the regulation of addictive behaviours and the neuropathology of drug dependence49,50.”
From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [50]
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“One of the most dramatic examples of protein expression induction is in the transcription factor ΔFosB, a Fos family protein, which accumulates in the NAc after chronic exposure to drugs of abuse, including alcohol, amphetamine, cannabinoids, cocaine, nicotine, opiates, and phencyclidine [86,87].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [87]
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Citations
Cites
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-citationAddiction, 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
Koob, G. F., Sanna, P. P., & Bloom, F. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)80557-7 · Cited by 1,026
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-citationGreengard, P., Allen, P. B., & Nairn, A. C. (1999) · Neuron · doi:10.1016/s0896-6273(00)80798-9 · Cited by 761
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
Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine
Kelz, M. B., Chen, J., Carlezon, W. A., Whisler, K., Gilden, L., Beckmann, A. M., Steffen, C., Zhang, Y.-J., Marotti, L., Self, D. W., et al. (1999) · Nature · doi:10.1038/45790 · Cited by 641
Self-citationHope, B. T., Nye, H. E., Kelz, M. B., Self, D. W., Iadarola, M. J., Nakabeppu, Y., Duman, R. S., & Nestler, E. J. (1994) · Neuron · doi:10.1016/0896-6273(94)90061-2 · Cited by 562
Self-citationPhosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons
Bibb, J. A., Snyder, G. L., Nishi, A., Yan, Z., Meijer, L., Fienberg, A. A., Tsai, L., Kwon, Y. T., Girault, J., Czernik, A. J., et al. (1999) · Nature · doi:10.1038/45251 · Cited by 553
Drug addiction: A model for the molecular basis of neural plasticity
Nestler, E. J., Hope, B. T., & Widnell, K. L. (1993) · Neuron · doi:10.1016/0896-6273(93)90213-b · Cited by 535
Self-citationCocaine induces striatal c-fos-immunoreactive proteins via dopaminergic D1 receptors.
Young, S., Porrino, L. J., & Iadarola, M. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.4.1291 · Cited by 497
DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission
Fienberg, A. A., Hiroi, N., Mermelstein, P. G., Song, W., Snyder, G. L., Nishi, A., Chéramy, A., O'Callaghan, J. P., Miller, D. B., Cole, D. G., et al. (1998) · Science · doi:10.1126/science.281.5378.838 · Cited by 496
Self-citationEffects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5
Bibb, J. A., Chen, J., Taylor, J. R., Svenningsson, P., Nishi, A., Snyder, G. L., Yan, Z., Sagawa, Z. K., Ouimet, C. C., Nairn, A. C., et al. (2001) · Nature · doi:10.1038/35066591 · Cited by 483
Self-citationHope, B. T., Kosofsky, B. E., Hyman, S. E., & Nestler, E. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.13.5764 · Cited by 474
Self-citationPostsynaptic organisation and regulation of excitatory synapses
Scannevin, R. H., & Huganir, R. L. (2000) · Nature reviews. Neuroscience · doi:10.1038/35039075 · Cited by 472
O’Donovan, K. J., Tourtellotte, W. G., Milbrandt, J., & Baraban, J. M. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01343-5 · Cited by 457
A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity
Nakabeppu, Y., & Nathans, D. (1991) · Cell · doi:10.1016/0092-8674(91)90504-r · Cited by 430
LTP mechanisms: from silence to four-lane traffic
Malinow, R., Mainen, Z. F., & Hayashi, Y. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00099-4 · Cited by 386
Common Neural Substrates for the Addictive Properties of Nicotine and Cocaine
Pich, E. M., Pagliusi, S. R., Tessari, M., Talabot‐Ayer, D., van Huijsduijnen, R. H., & Chiamulera, C. (1997) · Science · doi:10.1126/science.275.5296.83 · Cited by 347
Chronic Fos-Related Antigens: Stable Variants of ΔFosB Induced in Brain by Chronic Treatments
Chen, J., Kelz, M. B., Hope, B. T., Nakabeppu, Y., & Nestler, E. J. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-13-04933.1997 · Cited by 334
Self-citationRole of covalent modifications of histones in regulating gene expression
Spencer, V. A., & Davie, J. (1999) · Gene · doi:10.1016/s0378-1119(99)00405-9 · Cited by 306
White, F. J., Hu, X. T., Zhang, X., & Wolf, M. E. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09601-6 · Cited by 291
Hiroi, N., Brown, J. R., Haile, C. N., Ye, H., Greenberg, M. E., & Nestler, E. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10397 · Cited by 285
Self-citationMoratalla, R., Elibol, B., Vallejo, M., & Graybiel, A. M. (1996) · Neuron · doi:10.1016/s0896-6273(00)80288-3 · Cited by 276
Addiction to Cocaine and Amphetamine
Hyman, S. E. (1996) · Neuron · doi:10.1016/s0896-6273(00)80111-7 · Cited by 234
Immediate-early genes: ten years on
Morgan, J. I., & Curran, T. (1995) · Trends in Neurosciences · doi:10.1016/0166-2236(95)80022-t · Cited by 225
Nye, H. E., Hope, B. T., Kelz, M. B., Iadarola, M. J., & Nestler, E. J. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12232-5 · Cited by 207
Self-citationInduction of chronic Fos-related antigens in rat brain by chronic morphine administration.
Nye, H. E., & Nestler, E. J. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08777-2 · Cited by 205
Self-citationTransgenic animals with inducible, targeted gene expression in brain.
Chen, J.-S., Kelz, M., Zeng, G., Sakai, N., Steffen, C., Shockett, P. E., Picciotto, M., Duman, R., & Nestler, E. J. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.3.495 · Cited by 194
Self-citationRegulation of delta FosB and FosB-like proteins by electroconvulsive seizure and cocaine treatments.
Chen, J., Nye, H. E., Kelz, M. B., Hiroi, N., Nakabeppu, Y., Hope, B. T., & Nestler, E. J. (1995) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10546-4 · Cited by 149
Self-citationYen, J., Wisdom, R., Tratner, I., & Verma, I. M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.12.5077 · Cited by 143
Hiroi, N., Marek, G. J., Brown, J. R., Ye, H., Saudou, F., Vaidya, V. A., Duman, R. S., Greenberg, M. E., & Nestler, E. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-17-06952.1998 · Cited by 139
Self-citationShippenberg, T. S., & Rea, W. P. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(96)00450-9 · Cited by 130
Chen, J., Zhang, Y., Kelz, M. B., Steffen, C., Ang, E. S., Zeng, L., & Nestler, E. J. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-24-08965.2000 · Cited by 101
Self-citationDobrazanski, P., Noguchi, T., Kovary, K., Rizzo, C. A., Lazo, P. S., & Bravo, R. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.11.5470 · Cited by 97
ΔFosB: a molecular switch underlying long-term neural plasticity
Kelz, M. B., & Nestler, E. J. (2000) · Current Opinion in Neurology · doi:10.1097/00019052-200012000-00017 · Cited by 93
Self-citationOpiate and Cocaine Addictions: Challenge for Pharmacotherapies
Kreek, M. J. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(96)00440-6 · Cited by 86
Neuronal and behavioural abnormalities in striatal function in DARPP‐32‐mutant mice
Hiroi, N., Fienberg, A. A., Haile, C. N., Alburges, M. E., Hanson, G. R., Greengard, P., & Nestler, E. J. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00570.x · Cited by 81
Self-citationNAC-1 Is a Brain POZ/BTB Protein That Can Prevent Cocaine-Induced Sensitization in the Rat
Mackler, S. A., Korutla, L., Cha, X.-Y., Koebbe, M. J., Fournier, K. M., Bowers, M. S., & Kalivas, P. W. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06210.2000 · Cited by 78
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).
Cited by
Sorted by citations
The Neural Basis of Addiction: A Pathology of Motivation and Choice
Kalivas, P. W., & Volkow, N. D. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.8.1403 · Cited by 2,757
Chambers, R. A., Taylor, J. R., & Potenza, M. N. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.6.1041 · Cited by 1,719
“Similarly, addictive substances are collectively associated with chemical stimulation and neuroplastic changes in brain motivation substrates, leading to further drug use at the expense of social and occupational outcomes (15).”
BackgroundInfluentialIs there a common molecular pathway for addiction?
Nestler, E. J. (2005) · Nature Neuroscience · doi:10.1038/nn1578 · Cited by 1,388
Self-citationEpigenetic regulation in psychiatric disorders
Tsankova, N., Renthal, W., Kumar, A., & Nestler, E. J. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2132 · Cited by 1,400
Self-citationDiscovering Endophenotypes for Major Depression
Hasler, G., Drevets, W. C., Manji, H. K., & Charney, D. S. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300506 · Cited by 1,123
“Specifically, neurotrophic factors including cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) and the transcription factor delta-FosB may represent molecular mechanisms involved in long-term alterations of the brain reward system (Nestler et al, 2001, 2002).”
Background
Metadata
- 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
- Publisher
- National Academy of Sciences
- Published
- 2001-09-25
- Volume
- 98
- Issue
- 20
- Pages
- 11042-11046
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- 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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