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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Background
Gene expression profiling: methodological challenges, results, and prospects for addiction research
Pollock, J. D. (2002) · Chemistry and Physics of Lipids · doi:10.1016/s0009-3084(02)00160-3 · Cited by 51
Signal transduction in l-DOPA-induced dyskinesia: from receptor sensitization to abnormal gene expression
Spigolon, G., & Fisone, G. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1847-7 · Cited by 52
Unraveling the molecular mechanisms of alcohol dependence
Kalsi, G., Prescott, C. A., Kendler, K. S., & Riley, B. P. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.10.005 · Cited by 50
Neuroplasticity, axonal guidance and micro‐ RNA genes are associated with morphine self‐administration behavior
Tapocik, J. D., Luu, T. V., Mayo, C. L., Wang, B., Doyle, E., Lee, A. D., Lee, N. H., & Elmer, G. I. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00470.x · Cited by 53
Downregulation of Neuronal cdk5/p35 in Opioid Addicts and Opiate-Treated Rats: Relation to Neurofilament Phosphorylation
Ferrer‐Alcón, M., Harpe, R. L., Guimón, J., & Garcı́a-Sevilla, J. A. (2002) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300095 · Cited by 49
“…effects of cocaine on the cdk5/p35 complex (upregulation) were mediated through the induction of the transcription factor DFosB (Bibb et al, 2001), and the accumulation of DFosB in brain also has been observed after chronic morphine administration (Nye and Nestler, 1996; Nestler et al, 2001).”
Background
Proteomics in neurosciences
Drabik, A., Bierczyńska-Krzysik, A., Bodzoń‐Kułakowska, A., Suder, P., Kotlinska, J. H., & Silberring, J. (2007) · Mass Spectrometry Reviews · doi:10.1002/mas.20131 · Cited by 48
Activation of corticotropin releasing factor-containing neurons in the rat central amygdala and bed nucleus of the stria terminalis following exposure to two different anxiogenic stressors
Butler, R. K., Oliver, E. M., Sharko, A. C., Parrilla-Carrero, J., Kaigler, K. F., Fadel, J. R., & Wilson, M. A. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.01.051 · Cited by 46
The vagus nerve is necessary for the rapid and widespread neuronal activation in the brain following oral administration of psychoactive bacteria
Bharwani, A., West, C. L., Champagne-Jorgensen, K., Neufeld, K. M., Ruberto, J., Kunze, W., Bienenstock, J., & Forsythe, P. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108067 · Cited by 46
Patterns of Brain Activation Associated With Contextual Conditioning to Methamphetamine in Mice.
Rhodes, J. S., Ryabinin, A. E., & Crabbe, J. C. (2005) · Behavioral Neuroscience · doi:10.1037/0735-7044.119.3.759 · Cited by 49
Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats
Zhou, L.-F., & Zhu, Y.-P. (2006) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.2006.b0107 · Cited by 47
“A primary mechanism by which drugs of abuse affect gene expression is through changing the concentration of transcription factors in the nuclei of cells (Nestler et al., 2001).”
Background
Central losartan attenuates increases in arterial pressure and expression of FosB/ΔFosB along the autonomic axis associated with chronic intermittent hypoxia
Knight, W. D., Saxena, A., Shell, B., Nedungadi, T. P., Mifflin, S. W., & Cunningham, J. T. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00541.2012 · Cited by 45
Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine
Kharkwal, G., Radl, D. B., Lewis, R. G., & Borrelli, E. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1608362113 · Cited by 45
From Circuits to Chromatin: The Emerging Role of Epigenetics in Mental Health
Mews, P., Calipari, E. S., Day, J. J., Lobo, M. K., Bredy, T. W., & Abel, T. G. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.1649-20.2020 · Cited by 42
“Early studies investigating transcriptional changes in the NAc and other brain regions involved in reward discovered that the transcription factor D FosB becomes upregulated with chronic drug exposure (Nestler et al., 2001).”
Background
Overexpression Screen in Drosophila Identifies Neuronal Roles of GSK-3β/shaggyas a Regulator of AP-1-Dependent Developmental Plasticity
Franciscovich, A., Vrailas‐Mortimer, A. D., Freeman, A. A. H., Gu, J., & Sanyal, S. (2008) · Genetics · doi:10.1534/genetics.107.085555 · Cited by 47
“This intrinsic plasticity of neurons results in persistent modifications that are orchestrated by the synthesis of new proteins, either through translation of preexisting mRNA or activation of nuclear transcription (Nestler et al. 2001; West et al. 2001; Lonze and Ginty 2002; Klann et al. 2004).”
Background
Opiate Sensitization Induces FosB/ΔFosB Expression in Prefrontal Cortical, Striatal and Amygdala Brain Regions
Kaplan, G. B., Leite‐Morris, K. A., Fan, W., Young, A. J., & Guy, M. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023574 · Cited by 44
“Over-expression of DFosB in nucleus accumbens and dorsal striatum increased locomotor and rewarding responses to both cocaine and morphine [9,22,26].”
Background
Alterations of neuronal precursor cells in stages of human adult neurogenesis in heroin addicts
Bayer, R., Franke, H., Ficker, C., Richter, M., Lessig, R., Büttner, A., & Weber, M. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.09.005 · Cited by 47
“Learning and conditioning contributes to eroin tolerance and dependence as well as vulnerability to comulsive relapse (Altman et al., 1996; Eisch and Harburg, 2006; estler, 1993; Nestler et al., 2001).”
Background
Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABAB receptor
Jang, E. Y., Choe, E. S., Hwang, M., Kim, S. C., Lee, J. R., Kim, S. G., Jeon, J., Buono, R. J., & Yang, C. H. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.03.054 · Cited by 43
Addiction to Propofol
Earley, P. H., & Finver, T. (2013) · Journal of Addiction Medicine · doi:10.1097/adm.0b013e3182872901 · Cited by 42
“, 2011)—a putative signaling mechanism for most, if not all, addictive drugs (Nestler et al., 2001; Nestler, 2005, 2008).”
Background
In Vivo Bioluminescence Imaging Reveals Redox-Regulated Activator Protein-1 Activation in Paraventricular Nucleus of Mice With Renovascular Hypertension
Burmeister, M. A., Young, C. N., Braga, V. A., Butler, S. D., Sharma, R. V., & Davisson, R. L. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.160564 · Cited by 41
Dynamic DNA Methylation Regulates Levodopa-Induced Dyskinesia
Figge, D. A., Jaunarajs, K. L. E., & Standaert, D. G. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0683-16.2016 · Cited by 42
“For example, LID priming is known to be dependent on both the enhanced expression and alternative splicing of FosB causing sustained protein expression and increased AP-1 transcriptional activity (Nestler et al., 2001; Santini et al., 2009; Heiman et al., 2014).”
Background
Neuroanatomical specificity of conditioned responses to cocaine versus food in mice
Zombeck, J. A., Chen, G.-T., Johnson, Z. V., Rosenberg, D. M., Craig, A. B., & Rhodes, J. S. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.004 · Cited by 41
Inhibition by agmatine on morphine-induced conditioned place preference in rats
Wei, X.-L., Su, R., Lu, X., Liu, Y., Yu, S.-Z., Ben-li, Y., & Li, J. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.03.045 · Cited by 41
Early adolescent nicotine exposure affects later-life cocaine reward in mice
Alajaji, M., Lazenka, M. F., Kota, D., Wise, L. E., Younis, R. M., Carroll, F. I., Levine, A., Selley, D. E., Sim-Selley, L. J., & Damaj, M. I. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.032 · Cited by 39
“One mechanism that could underlie these adaptations is induction of DFosB, a stable transcription factor that accumulates with repeated drug exposure (Chen et al., 1997; Nestler et al., 2001).”
Background
The effect of various morphine weaning regimens on the sequelae of opioid tolerance involving physical dependency, anxiety and hippocampus cell neurodegeneration in rats
Motaghinejad, M., Karimian, S. M., Motaghinejad, O., Shabab, B., Asadighaleni, M., & Fatima, S. (2015) · Fundamental & Clinical Pharmacology · doi:10.1111/fcp.12121 · Cited by 45
Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice
Soto, J. S., Neupane, C., Kaur, M., Pandey, V., Wohlschlegel, J. A., & Khakh, B. S. (2024) · Neuron · doi:10.1016/j.neuron.2024.07.019 · Cited by 43
Role of striatal ΔFosB in l -Dopa–induced dyskinesias of parkinsonian nonhuman primates
Beck, G., Singh, A. P., Zhang, J., Potts, L. F., Woo, J.-M., Park, E. S., Mochizuki, H., Mouradian, M. M., & Papa, S. M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907810116 · Cited by 40
Cell Type–Specific Whole-Genome Landscape of ΔFOSB Binding in the Nucleus Accumbens After Chronic Cocaine Exposure
Yeh, S.-Y., Estill, M. S., Lardner, C. K., Browne, C. J., Minier-Toribio, A. M., Futamura, R., Beach, K., McManus, C. A., Xu, S., Zhang, S., et al. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.12.021 · Cited by 35
Self-citation
Epigenetic regulation in drug addiction.
Biliński, P., Wojtyła, A., Kapka‐Skrzypczak, L., Chwedorowicz, R., Cyranka, M., & Studziński, T. (2012) · PubMed · Cited by 39
Knockdown of tyrosine hydroxylase in the nucleus of the solitary tract reduces elevated blood pressure during chronic intermittent hypoxia
Bathina, C. S., Rajulapati, A., Franzke, M., Yamamoto, K., Cunningham, J. T., & Mifflin, S. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00260.2013 · Cited by 39
Comparison of the activation of somatostatin- and neuropeptide Y-containing neuronal populations of the rat amygdala following two different anxiogenic stressors
Butler, R. K., White, L. C., Frederick-Duus, D., Kaigler, K. F., Fadel, J. R., & Wilson, M. A. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.08.002 · Cited by 42
“The two hour time point was chosen because that is within the 1–3 h post-exposure time frame in which c-Fos is maximally expressed (Nestler et al., 2001) and to maintain consistency with our previous studies (Butler et al., 2011).”
Result
Running in laboratory and wild rodents: Differences in context sensitivity and plasticity of hippocampal neurogenesis
Klaus, F., & Amrein, I. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.04.027 · Cited by 40
Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis
Sharko, A. C., Kaigler, K. F., Fadel, J. R., & Wilson, M. A. (2015) · Alcohol · doi:10.1016/j.alcohol.2015.11.001 · Cited by 39
The biology of addiction
MacNicol, B. J. (2016) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/s12630-016-0771-2 · Cited by 52
Sex- and dose-dependent abuse liability of repeated subanesthetic ketamine in rats
Schoepfer, K. J., Strong, C. E., Saland, S. K., Wright, K. N., & Kabbaj, M. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.10.021 · Cited by 38
“The transcription factor ΔFosB is stably upregulated in the NAc following chronic treatment with various drugs of abuse, where, as a component of the AP-1 complex with JunD, it is transcriptionally active and regulates relevant behavioral plasticities [45,46,48,50,84].”
Background
Sleep loss and addiction
López-Muciño, L. A., García‐García, F., Cueto‐Escobedo, J., Acosta-Hernández, M. E., Venebra-Muñoz, A., & Rodríguez‐Alba, J. C. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104832 · Cited by 41
Addicted to palatable foods: comparing the neurobiology of Bulimia Nervosa to that of drug addiction
Hadad, N. A., & Knackstedt, L. A. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3461-1 · Cited by 42
“The release of DA and subsequent stimulation of D1 receptors in the NAc occurring upon administration of addictive drugs produces a signaling cascade that includes an increase in expression of transcription factors such asΔFosB (for review, see Nestler et al. 2001).”
Background
Long-term ethanol self-administration induces ΔFosB in male and female adolescent, but not in adult, Wistar rats
Wille‐Bille, A., de Olmos, S., Marengo, L. G., Chiner, F., & Pautassi, R. M. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.11.008 · Cited by 38
Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas
Rawas, R. E., Klement, S., Salti, A., Fritz, M., Dechant, G., Saria, A., & Zernig, G. (2012) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2012.00008 · Cited by 37
“One of these adaptations is an altered expression of transcription factors that engender changes in gene expression and may possibly lead to alterations in sensitivity to drugs of abuse (Hyman and Malenka, 2001; Nestler et al., 2001).”
Background
Chronic exercise increases sensitivity to the conditioned rewarding effects of cocaine.
Smith, M. A., Gergans, S. R., Iordanou, J. C., & Lyle, M. A. (2008) · PubMed · Cited by 37
Parabrachial Calca neurons drive nociplasticity
Condon, L. F., Yu, Y., Park, S., Cao, F., Pauli, J. L., Nelson, T. S., & Palmiter, R. D. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114057 · Cited by 41
Experimental Psychiatric Illness and Drug Abuse Models: From Human to Animal, an Overview
Edwards, S., & Koob, G. F. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-458-2_2 · Cited by 37
Role of dorsal hippocampal orexin-1 receptors in associating morphine reward with contextual stimuli
Riahi, E., Khodagholi, F., & Haghparast, A. (2013) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3283635ee9 · Cited by 36
“The expression of c-Fos frequently peaks 1.5–2 h after acute drug administration and usually returns to the baseline after 6 h (Nestler et al., 2001).”
BackgroundInfluential

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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