Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens
Open accessAbstract
An important issue in affective neuroscience concerns the role of mesocorticolimbic dopamine systems in positive-valenced motivation (e.g., reward) versus negative-valenced motivation (e.g., fear). Here, we assessed whether endogenous dopamine receptor stimulation in nucleus accumbens contributes to both appetitive behavior and fearful behavior that is generated in keyboard manner by local glutamate disruptions at different sites in medial shell. 6,7-Dinitroquinoxaline-2,3(1 H,4 H)-dione (DNQX) microinjections (450 ng) locally disrupt glutamate signals in <4 mm 3 of nucleus accumbens, and generate either desire or fear (or both) depending on precise rostrocaudal location in medial shell. At rostral shell sites, local AMPA/kainate blockade generates positive ingestive behavior, but the elicited motivated behavior becomes incrementally more fearful as the same microinjection is moved caudally. A dopamine-blocking mixture of D 1 and D 2 antagonists (raclopride and SCH-23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1 H-3-benzazepine hydrochloride]) was combined here in the same microinjection with DNQX to assess the role of endogenous local dopamine in mediating the DNQX-motivated behaviors. We report that local dopamine blockade prevented DNQX microinjections from generating appetitive behavior (eating) in rostral shell, and equally prevented DNQX from generating fearful behavior (defensive treading) in caudal shell. We conclude that local dopamine is needed to enable disruptions of corticolimbic glutamate signals in shell to generate either positive incentive salience or negative fearful salience (valence depending on site and other conditions). Thus, dopamine interacts with localization of valence-biased glutamate circuits in medial shell to facilitate keyboard stimulation of both appetitive and fearful motivations.
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DA is actively involved in aversive motivation like escape behavior.
“Research also suggests DA is actively involved in aversive motivation like escape behavior (Faure et al., 2008;Salamone, 1992).”
From Physiological feelings (2019) · cites this paper as Faure et al., 2008
The Results section, “Dopamine antagonists prevent caudal elicitation of fear” (page unavailable), reports that blocking dopamine receptors prevented DNQX-induced defensive treading in rats. This supports dopamine’s involvement in aversive motivation under the tested conditions, but the paper did not test escape behavior specifically. (LLM, conf=0.86)
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The bivalent side of the nucleus accumbens
Levita, L., Hare, T. A., Voss, H. U., Glover, G., Ballon, D. J., & Casey, B. J. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2008.09.039 · Cited by 117 · see citing works
Faure, A., Richard, J. M., & Berridge, K. C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011223 · Cited by 114 · see citing works
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Enhancement stimulants: perceived motivational and cognitive advantages
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Maternal Behavior: Neural Circuits, Stimulus Valence, and Motivational Processes
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- Authors
- Faure, A., Reynolds, S. M., Richard, J. M., & Berridge, K. C.
- Affiliations
- University of Michigan (US)
- Université Paris-Sud (FR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-07-09
- Volume
- 28
- Issue
- 28
- Pages
- 7184-7192
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2519054
- OpenAlex
- W2106767458
- Cited by
- 193
- References
- 77
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 11 · 2018: 12 · 2017: 10 · 2016: 13 · 2015: 14 · 2014: 14 · 2013: 20 · 2012: 19
- FWCI
- 7.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH-63649, R01MH063649)
- National Institute on Drug Abuse (DA15188, R01DA015188)
- 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
- mesolimbic dopamine system, DNQX, appetitive motivation, fear, incentive salience, valence
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Dopamine, Drug Interactions, Fear, Feeding Behavior, Limbic System, Male, Microinjections, Motivation, Nucleus Accumbens, Dopamine Agents, Gene Expression, Oncogene Proteins v-fos, Rats, Sprague-Dawley, Excitatory Amino Acid Agents, Glutamic Acid, Rats
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