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Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward
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The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease.
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“Rather, activation of dynorphin cells can produce either aversive or reinforcing outcomes in a region specific manner (77), suggesting heterogeneous populations of striatal MSNs may drive depression symptomology differentially as well.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [77]
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“Rather, activation of dynorphin cells can produce either aversive or reinforcing outcomes in a region specific manner (77), suggesting heterogeneous populations of striatal MSNs may drive depression symptomology differentially as well.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [77]
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Metadata
- Authors
- Al-Hasani, R., McCall, J. G., Shin, G., Gomez, A. M., Schmitz, G. P., Bernardi, J. M., Pyo, C.-O., Park, S. I., Marcinkiewcz, C. M., Crowley, N. A., Krashes, M. J., Lowell, B. B., Kash, T. L., Rogers, J. A., & Bruchas, M. R.
- Affiliations
- Washington University in St. Louis (US)
- University of Illinois Urbana-Champaign (US)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Bruchas, Michael R.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 87
- Issue
- 5
- Pages
- 1063-1077
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4625385
- OpenAlex
- W1919448202
- Cited by
- 345
- References
- 65
- Citations by year
- 2026: 16 · 2025: 33 · 2024: 28 · 2023: 30 · 2022: 32 · 2021: 36 · 2020: 42 · 2019: 40 · 2018: 34 · 2017: 25 · 2016: 26 · 2015: 3
- FWCI
- 13.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Hope Center for Neurological Disorders
- National Institutes of Health (K99-R00, DA033396)
- National Institute on Alcohol Abuse and Alcoholism (P60AA011605)
- National Institute of Mental Health (K99/R00, F31MH101956)
- National Institute on Drug Abuse (R01DA033396, DA033396, K99DA038725, R01DA037152, DA038725, R00DA038725)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075632, R01DK089044, R01DK071051, P30DK046200, R01DK096010, R37DK053477)
- National Institute of Neurological Disorders and Stroke (TR01NS081707, P30NS057105, R01NS081707, K99/R00)
- National Center for Research Resources (S10RR027552)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- nucleus accumbens shell, kappa opioid receptor, aversive behavior, place preference, reward, photostimulation, regional specificity, motivated behavior, dysphoria
- MeSH terms
- Action Potentials, Animals, Avoidance Learning, Conditioning, Operant, Dynorphins, Electric Stimulation, Gene Expression Regulation, Luminescent Proteins, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Nucleus Accumbens, Photic Stimulation, Protein Precursors, Reward, Self Stimulation, Time Factors, Receptors, Dopamine D2, Maze Learning, Mice, Wireless Technology, In Vitro Techniques
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