NMDA receptor antagonism in the basolateral but not central amygdala blocks the extinction of Pavlovian fear conditioning in rats

Zimmerman, Joshua M.; Maren, Stephen

doi:10.1111/j.1460-9568.2010.07223.x

Cited by 127Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

NMDA receptor antagonism in the basolateral but not central amygdala blocks the extinction of Pavlovian fear conditioning in rats

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Zimmerman, Joshua M., Maren, Stephen·2010·European Journal of Neuroscience

DOI 10.1111/j.1460-9568.2010.07223.xPMC PMC3901015

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Abstract

Glutamate receptors in the basolateral complex of the amygdala (BLA) are essential for the acquisition, expression and extinction of Pavlovian fear conditioning in rats. Recent work has revealed that glutamate receptors in the central nucleus of the amygdala (CEA) are also involved in the acquisition of conditional fear, but it is not known whether they play a role in fear extinction. Here we examine this issue by infusing glutamate receptor antagonists into the BLA or CEA prior to the extinction of fear to an auditory conditioned stimulus (CS) in rats. Infusion of the α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA) receptor antagonist, 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo[f]quinoxaline‐2,3‐dione (NBQX), into either the CEA or BLA impaired the expression of conditioned freezing to the auditory CS, but did not impair the formation of a long‐term extinction memory to that CS. In contrast, infusion of the N‐methyl‐d‐aspartate (NMDA) receptor antagonist, d,l‐2‐amino‐5‐phosphonopentanoic acid (APV), into the amygdala, spared the expression of fear to the CS during extinction training, but impaired the acquisition of a long‐term extinction memory. Importantly, only APV infusions into the BLA impaired extinction memory. These results reveal that AMPA and NMDA receptors within the amygdala make dissociable contributions to the expression and extinction of conditioned fear, respectively. Moreover, they indicate that NMDA receptor‐dependent processes involved in extinction learning are localized to the BLA. Together with previous work, these results reveal that NMDA receptors in the CEA have a selective role acquisition of fear memory.

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Both fear learning and extinction are blocked by antagonists at the glutamatergic NMDA receptor.
“Both fear learning and extinction are blocked by antagonists at the glutamatergic NMDA receptor (Zimmerman and Maren, 2010).”
From D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial (2014) · cites this paper as Zimmerman and Maren, 2010

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Authors: Zimmerman, J. M., & Maren, S.
Affiliations: University of Michigan (US)
ORCID: Zimmerman, Joshua M.
Maren, Stephen
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2010-04-30
Volume: 31
Issue: 9
Pages: 1664-1670
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1111/j.1460-9568.2010.07223.x
PMC: PMC3901015
OpenAlex: W1790006082
Cited by: 127
References: 48
Citations by year: 2026: 2 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 5 · 2019: 8 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 16 · 2014: 16 · 2013: 12 · 2012: 6
FWCI: 5.03
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Deep Blue (University of Michigan) (acceptedVersion)
Funders: National Institute of Mental Health (R01MH073655, R01MH065961)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: NMDA receptor antagonism, AMPA receptor antagonism, basolateral amygdala, central amygdala, fear extinction, fear conditioning, memory extinction, conditioned freezing, APV, NBQX, glutamate receptors, auditory conditioned stimulus
MeSH terms: Acoustic Stimulation, Amygdala, Animals, Auditory Perception, Conditioning, Classical, Extinction, Psychological, Fear, Male, Memory, Quinoxalines, Valine, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Receptors, AMPA, Excitatory Amino Acid Antagonists, Rats, Long-Evans, Freezing Reaction, Cataleptic, Rats

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NMDA receptor antagonism in the basolateral but not central amygdala blocks the extinction of Pavlovian fear conditioning in rats

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