Differential effects of the N-methyl-d-aspartate antagonist DL-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues

Fanselow, Michael S.; Kim, Jeansok J.; Yipp, Jon; De Oca, Beatrice

doi:10.1037/0735-7044.108.2.235

Cited by 142Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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Differential effects of the N-methyl-d-aspartate antagonist DL-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues

Fanselow, Michael S., Kim, Jeansok J., Yipp, Jon, De Oca, Beatrice·1994·Behavioral Neuroscience

DOI 10.1037/0735-7044.108.2.235

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Abstract

Intracerebroventricular (icv) administration of the N-methyl-D-aspartate receptor (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) before tone-shock pairings caused a dose-dependent suppression of acquisition of fear of contextual cues associated with shock. Acquisition of fear of the tone was not impaired. Experiment 2 showed that the fear of the tone was associative and that this tone-shock association was less affected by APV than was a context-shock association. Rats receiving APV before context-shock pairings showed an equivalent loss of fear regardless of whether testing occurred 1 or 28 days after training. It appears that icv administration of APV blocks acquisition of context conditioning by affecting NMDA receptors in the hippocampus. Activity at these receptors at the time of acquisition seems critical for later expression of both intermediate (1 day to 2 weeks) and remote (4 weeks) fear memories.

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Contextual fear conditioning requires the hippocampus, whereas cued fear conditioning does not.
“In addition, the finding that withdrawal disrupted contextual but not cued fear conditioning adds to a growing literature that, at least in the mouse model, nicotine withdrawal disrupts hippocampus-dependent learning but not hippocampus-independent learning as contextual fear conditioning requires the hippocampus whereas cued fear conditioning does not (Fanselow et al., 1994; Logue et al., 1997;”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Fanselow et al., 1994
Nicotine withdrawal disrupts hippocampus-dependent learning but not hippocampus-independent learning.
“In addition, the finding that withdrawal disrupted contextual but not cued fear conditioning adds to a growing literature that, at least in the mouse model, nicotine withdrawal disrupts hippocampus-dependent learning but not hippocampus-independent learning as contextual fear conditioning requires the hippocampus whereas cued fear conditioning does not (Fanselow et al., 1994; Logue et al., 1997;”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Fanselow et al., 1994
Contextual fear conditioning depends on the hippocampus, while cued fear conditioning does not.
“fear conditioning requires the hippocampus whereas cued fear conditioning does not (Fanselow et al., 1994; Logue et al., 1997; Phillips and Ledoux, 1992).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Fanselow et al., 1994

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Authors: Fanselow, M. S., Kim, J. J., Yipp, J., & De Oca, B.
Affiliations: University of California, Los Angeles (US)
ORCID: Fanselow, Michael S.
Kim, Jeansok J.
Venue: Behavioral Neuroscience
Publisher: American Psychological Association (APA)
Published: 1994
Volume: 108
Issue: 2
Pages: 235-240
ISSN: 0735-7044 (ISSN-L)
1939-0084
DOI: 10.1037/0735-7044.108.2.235
OpenAlex: W1969089790
Cited by: 142
References: 28
Citations by year: 2026: 1 · 2025: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 6 · 2012: 2
FWCI: 2.58
Type: journal article
Language: en
Open access: closed
Locations: Behavioral Neuroscience (publishedVersion)
PubMed (publishedVersion)
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, fear conditioning, contextual fear, hippocampus, memory consolidation, remote memory, intracerebroventricular administration, associative learning
MeSH terms: Animals, Association Learning, Auditory Perception, Conditioning, Classical, Cues, Dose-Response Relationship, Drug, Electroshock, Fear, Female, Hippocampus, Memory, Short-Term, Motor Activity, Mental Recall, Retention, Psychology, Social Environment, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Rats

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Differential effects of the N-methyl-d-aspartate antagonist DL-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues

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