Cited by 110Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionStress Responses and Cortisol

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Role of the Brain's Reward Circuitry in Depression

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Nestler, Eric J.·2015·International review of neurobiology

DOI 10.1016/bs.irn.2015.07.003PMC PMC4690450

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Abstract

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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The Neurobiology of Resilience
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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)
DOI: 10.1016/bs.irn.2015.07.003
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Role of the Brain's Reward Circuitry in Depression

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