The DOI matches its Crossref record; 134 of the 134 references it cites were found in a registry or an index.
Biological substrates of reward and aversion: A nucleus accumbens activity hypothesis
Open accessAbstract
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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“Moreover, the striatum and associated DA systems play a prominent role in processing aversive stimuli and processing rewards [741,742].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [741]
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Dopamine: Functions, Signaling, and Association with Neurological Diseases
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Metadata
- Authors
- Carlezon, W. A., & Thomas, M. J.
- Affiliations
- Harvard University (US)
- University of Minnesota (US)
- Corresponding author
- Carlezon, William A.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 56
- Pages
- 122-132
- ISSN
- 0028-3908 (ISSN-L)
- 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
- 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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