Blockade of dopamine activity in the nucleus accumbens impairs learning extinction of conditioned fear
Open accessAbstract
Three experiments used rats to investigate the role of dopamine activity in learning to inhibit conditioned fear responses (freezing) in extinction. In Experiment 1, rats systemically injected with the D2 dopamine antagonist, haloperidol, froze more across multiple extinction sessions and on a drug-free retention test than control rats. In Experiment 2, rats extinguished under an intracerebroventricular (ICV) infusion of haloperidol suppressed fear responses across extinction but froze more on a subsequent drug-free retention test than control rats. In Experiment 3, rats extinguished under an infusion of haloperidol in the nucleus accumbens were impaired in suppressing fear responses across extinction and froze more on subsequent drug-free retention test than control rats. These results show that learning to inhibit fear responses in extinction requires dopamine activity in the nucleus accumbens. They were interpreted to mean that dopaminergic activity in the nucleus accumbens regulates the prediction error required for learning to inhibit fear responses in extinction.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Administration of the D2-dopamine receptor antagonist haloperidol in the nucleus accumbens (NAc) impaired suppression of fear responses after extinction.
“administration of the D2-dopamine receptor antagonist, haloperidol, in the nucleus accumbens (NAc) impaired suppression of fear responses after extinction (Holtzman-Assif et al., 2010).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Holtzman-Assif et al., 2010
Dopaminergic activity plays a role in extinction learning, with the NAc as a critical locus for learning and retention of the inhibition created by fear extinction training.
“This evidence supports the role of dopaminergic activity in extinction learning and especially pointing towards the NAc as a critical locus for learning and retention of the inhibition created by fear extinction training (Holtzman-Assif et al., 2010).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Holtzman-Assif et al., 2010
Cites
Neurons in medial prefrontal cortex signal memory for fear extinction
Milad, M. R., & Quirk, G. J. (2002) · Nature · doi:10.1038/nature01138 · Cited by 1,836 · cited 1× · see citing works
“In contrast, the infralimbic (IL) subregion of the mPFC is required for consolidation and retrieval of that inhibition (Quirk et al. 2000; Milad and Quirk 2002; Santini et al. 2004; Hugues et al. 2006; Sierra-Mercado et al. 2006; Burgos-Robles et al. 2007; Laurent and Westbrook 2008, 2009;…”
BackgroundNeural Mechanisms of Extinction Learning and Retrieval
Quirk, G. J., & Mueller, D. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301555 · Cited by 1,645 · see citing works
The role of ventromedial prefrontal cortex in the recovery of extinguished fear
Quirk, G. J., Russo, G. K., Barron, J. L., & Lebron, K. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06225.2000 · Cited by 957 · cited 1× · see citing works
“In contrast, the infralimbic (IL) subregion of the mPFC is required for consolidation and retrieval of that inhibition (Quirk et al. 2000; Milad and Quirk 2002; Santini et al. 2004; Hugues et al. 2006; Sierra-Mercado et al. 2006; Burgos-Robles et al. 2007; Laurent and Westbrook 2008, 2009;…”
BackgroundThe Neuroscience of Mammalian Associative Learning
Fanselow, M. S., & Poulos, A. M. (2005) · Annual Review of Psychology · doi:10.1146/annurev.psych.56.091103.070213 · Cited by 683 · see citing works
Contextual and temporal modulation of extinction: behavioral and biological mechanisms
Bouton, M. E., Westbrook, R. F., Corcoran, K. A., & Maren, S. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.12.015 · Cited by 671 · see citing works
Self-citationSynaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning
Blair, H. T., Schafe, G. E., Bauer, E. P., Rodrigues, S. M., & LeDoux, J. E. (2001) · Learning & Memory · doi:10.1101/lm.30901 · Cited by 610 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neural and cellular mechanisms of fear and extinction memory formation
Orsini, C. A., & Maren, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.12.014 · Cited by 429 · see citing works
Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A., & Ressler, K. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.004 · Cited by 390 · see citing works
“Brain Zn2+ signaling which, in addition to the NMDAR binding site, acts via other sites including the GPR39 Znsensing receptor (Holst et al., 2007), has been shown to exert both enhancing and attenuating effects on learning and memory via complex interactionswithneurotransmitters and synaptic…”
BackgroundFear extinction requires infralimbic cortex projections to the basolateral amygdala
Bloodgood, D. W., Sugam, J. A., Holmes, A., & Kash, T. L. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0106-x · Cited by 229 · see citing works
Wenzel, J. M., Rauscher, N. A., Cheer, J. F., & Oleson, E. B. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn500255p · Cited by 131 · see citing works
Prefrontal Dopaminergic Mechanisms of Extinction in Adolescence Compared to Adulthood in Rats
Zbukvic, I. C., Park, C. H. J., Ganella, D. E., Lawrence, A. J., & Kim, J. H. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00032 · Cited by 57 · see citing works
Vaverková, Z., Milton, A. L., & Merlo, E. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.574358 · Cited by 27 · see citing works
“It has also been shown that administration of the D2-dopamine receptor antagonist, haloperidol, in the nucleus accumbens (NAc) impaired suppression of fear responses after extinction (Holtzman-Assif et al., 2010).”
BackgroundInfluential
- Authors
- Holtzman-Assif, O., Laurent, V., & Westbrook, R. F.
- Affiliations
- UNSW Sydney (AU)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-02
- Volume
- 17
- Issue
- 2
- Pages
- 71-75
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- OpenAlex
- W2170041171
- Cited by
- 96
- References
- 6
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 12 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 6
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- dopamine, nucleus accumbens, fear extinction, fear conditioning, haloperidol, freezing behavior, prediction error, extinction retention, intracerebroventricular infusion
- MeSH terms
- Animals, Conditioning, Classical, Dopamine, Dose-Response Relationship, Drug, Extinction, Psychological, Fear, Haloperidol, Inhibition, Psychological, Injections, Intraventricular, Male, Nucleus Accumbens, Rats, Wistar, Dopamine Antagonists, Freezing Reaction, Cataleptic, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
