Cited by 345Neuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Distinct subpopulations of nucleus accumbens dynorphin neurons drive aversion and reward

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Al-Hasani, Ream, McCall, Jordan G., Shin, Gunchul, Gomez, Adrian M., Schmitz, Gavin P., Bernardi, Julio M., Pyo, Chang-O., Park, Sung Il +7 more·2015·Neuron

Abstract

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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Crossref · 10.1016/j.neuron.2015.08.019

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  • Activation of dynorphin cells can produce either aversive or reinforcing outcomes in a region-specific manner.

    “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.”
  • Heterogeneous populations of striatal medium spiny neurons may drive depression symptomology differentially.

    “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.”

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Research works printed but not linked: 2

  1. Al-Hasani R McCall JG Foshage AM Bruchas MR Locus coeruleus kappa-opioid receptors modulate reinstatement of cocaine place preference through a noradrenergic mechanism. Neuropsychopharmacology 2013b 38 2484 2497 23787819 PMC3799068
  2. Siuda ER Copits BA Schmidt MJ Baird MA Al-Hasani R Planer WJ Funderburk SC McCall JG Gereau RW 4th Bruchas MR Spatiotemporal control of opioid signaling and behavior. Neuron 2015b 86 923 935 25937173 PMC4441608

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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.
Venue
Neuron
Publisher
Elsevier BV
Published
2015-09
Volume
87
Issue
5
Pages
1063-1077
ISSN
0896-6273 (ISSN-L)
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
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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