The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Role of the Brain's Reward Circuitry in Depression
Open accessAbstract
Increasing evidence supports an important role for the brain's reward circuitry in controlling mood under normal conditions and contributing importantly to the pathophysiology and symptomatology of a range of mood disorders, such as depression. Here we focus on the nucleus accumbens (NAc), a critical component of the brain's reward circuitry, in depression and other stress-related disorders. The prominence of anhedonia, reduced motivation, and decreased energy level in most individuals with depression supports the involvement of the NAc in these conditions. We concentrate on several transcription factors (CREB, ΔFosB, SRF, NFκB, and β-catenin), which are altered in the NAc in rodent depression models--and in some cases in the NAc of depressed humans, and which produce robust depression- or antidepressant-like effects when manipulated in the NAc in animal models. These studies of the NAc have established novel approaches toward modeling key symptoms of depression in animals and could enable the development of antidepressant medications with fundamentally new mechanisms of action.
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“In rodent models of depression and depressive-like behaviors, multiple behavioral assays in addition to social interaction test, including sucrose preference, tail suspension, and forced swim tests are often used [7, 20, 29].”
From A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors (2026) · cites this paper as [29]
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“It has been described that a number of brain regions, such as the frontal cortex and the hippocampus, provide glutamatergic input to the VTA and NAc (Nestler, 2015).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Nestler, 2015
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“Our results also expand on other previous work implicating mPFC dysfunction in depression [7, 9, 29, 30]”
From A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors (2026) · cites this paper as [29]
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“The VC/VS is a central hub in the reward circuitry with dopaminergic inputs from the ventral tegmental area (VTA), and serving as a relay between prefrontal cortex (OFC, vmPFC, ACC), ventral striatum and the amygdala and hippocampus [55,56] (Fig. 4).”
From Deep brain stimulation for depression. (2022) · cites this paper as [55]
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Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
Diagnostic and Statistical Manual of Mental Disorders
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The Neuroendocrinology of Stress: A Never Ending Story
Lightman, S. L. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01711.x · Cited by 3,588
A Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375
Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217
Self-citationDrug Addiction, Dysregulation of Reward, and Allostasis
Koob, G. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00195-0 · Cited by 2,953
NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory
Hyman, S. E., Malenka, R. C., & Nestler, E. J. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.113009 · Cited by 2,647
Self-citationKrishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307
Self-citationEssential role of BDNF in the mesolimbic dopamine pathway in social defeat stress
Berton, O., McClung, C. A., DiLeone, R. J., Krishnan, V., Renthal, W., Russo, S. J., Graham, D., Tsankova, N. M., Bolanos, C. A., Rios, M., et al. (2006) · Science · doi:10.1126/science.1120972 · Cited by 2,129
Self-citationThe mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059
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The menace of obesity to depression and anxiety prevalence
Fulton, S., Décarie-Spain, L., Fioramonti, X., Guiard, B., & Nakajima, S. (2022) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2021.10.005 · Cited by 441
“In contrast, increasing brain-derived neurotrophic factor in the nucleus accumbens or ventral tegmental area produces a depressive-like phenotype, whereas animals with selective knockout of brain-derived neurotrophic factor in ventral tegmental area are protected from depressive effects produced by social defeat stres…”
BackgroundNeurobiology of Resilience: Interface Between Mind and Body
Cathomas, F., Murrough, J. W., Nestler, E. J., Han, M.-H., & Russo, S. J. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.04.011 · Cited by 296
Self-citationCircuit Mechanisms of Reward, Anhedonia, and Depression
Höflich, A., Michenthaler, P., Kasper, S., & Lanzenberger, R. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyy081 · Cited by 253
Goodwill, H. L., Manzano-Nieves, G., Gallo, M. E., Lee, H.-I., Oyerinde, E., Serre, T., & Bath, K. G. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0195-5 · Cited by 233
Bolton, J. L., Molet, J., Regev, L., Chen, Y., Rismanchi, N., Haddad, E., Yang, D. Z., Obenaus, A., & Baram, T. Z. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.023 · Cited by 222
Metadata
- Authors
- Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Nestler, Eric J.
- ORCID
- Nestler, Eric J.
- Venue
- International review of neurobiology
- Publisher
- Elsevier
- Published
- 2015
- Volume
- 124
- Pages
- 151-170
- ISSN
- 0074-7742 (ISSN-L)
- PMC
- PMC4690450
- OpenAlex
- W2410587014
- Cited by
- 108
- References
- 78
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 12 · 2023: 12 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 13 · 2018: 11 · 2017: 9 · 2016: 5
- FWCI
- 23.77
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International review of neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (P50MH096890, R01MH051399)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, reward systems, nucleus accumbens, anhedonia, stress-related disorders, transcription factors, CREB, ΔFosB, SRF, NF-κB, β-catenin, antidepressant mechanism, animal models of depression, mood disorders
- MeSH terms
- Animals, Brain, Depression, Disease Models, Animal, Gene Expression Regulation, Humans, Neural Pathways, Reward, Transcription Factors
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