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Biological substrates of reward and aversion: A nucleus accumbens activity hypothesis

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Carlezon, William A., Thomas, Mark J.·2009·Neuropharmacology

DOI 10.1016/j.neuropharm.2008.06.075PMC PMC2635333

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Abstract

The nucleus accumbens (NAc) is a critical element of the mesocorticolimbic system, a brain circuit implicated in reward and motivation. This basal forebrain structure receives dopamine (DA) input from the ventral tegmental area (VTA) and glutamate (GLU) input from regions including the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP). As such, it integrates inputs from limbic and cortical regions, linking motivation with action. The NAc has a well-established role in mediating the rewarding effects of drugs of abuse and natural rewards such as food and sexual behavior. However, accumulating pharmacological, molecular, and electrophysiological evidence has raised the possibility that it also plays an important (and sometimes underappreciated) role in mediating aversive states. Here we review evidence that rewarding and aversive states are encoded in the activity of NAc medium spiny GABAergic neurons, which account for the vast majority of the neurons in this region. While admittedly simple, this working hypothesis is testable using combinations of available and emerging technologies, including electrophysiology, genetic engineering, and functional brain imaging. A deeper understanding of the basic neurobiology of mood states will facilitate the development of well-tolerated medications that treat and prevent addiction and other conditions (e.g., mood disorders) associated with dysregulation of brain motivation systems.

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Authors: Carlezon, W. A., & Thomas, M. J.
Affiliations: Harvard University (US)
University of Minnesota (US)
Corresponding author: Carlezon, William A.
ORCID: Carlezon, William A.
Thomas, Mark J.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2009-01
Volume: 56
Pages: 122-132
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2008.06.075
PMC: PMC2635333
OpenAlex: W1977266070
Cited by: 561
References: 131
Citations by year: 2026: 11 · 2025: 17 · 2024: 21 · 2023: 17 · 2022: 12 · 2021: 22 · 2020: 31 · 2019: 63 · 2018: 25 · 2017: 31 · 2016: 32 · 2015: 33 · 2014: 44 · 2013: 45 · 2012: 47
FWCI: 3.05
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (R01DA012736, R01DA019666, DA019666, DA012736)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: nucleus accumbens, reward, aversion, aversive states, mesocorticolimbic system, medium spiny neurons, GABAergic neurons, dopamine, glutamate, ventral tegmental area, prefrontal cortex, amygdala, hippocampus, motivation, addiction, mood disorders, drug reward
MeSH terms: Animals, Avoidance Learning, Nucleus Accumbens, Reward, Illicit Drugs

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Biological substrates of reward and aversion: A nucleus accumbens activity hypothesis

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