Cited by 3,640Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeurotransmitter Receptor Influence on Behavior

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Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5

Morris, R. G. M., Anderson, E., Lynch, G. S., Baudry, M.·1986·Nature

DOI 10.1038/319774a0

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Abstract

Recent work has shown that the hippocampus contains a class of receptors for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate (NMDA) and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization. Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation. We now report that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning, which is not. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. These results suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis that LTP is involved in some, but not all, forms of learning.

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Authors: Morris, R. G. M., Anderson, E., Lynch, G. S., & Baudry, M.
Affiliations: University of St Andrews (GB)
University of California, Irvine (US)
ORCID: Morris, R. G. M.
Lynch, G. S.
Baudry, M.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1986-02
Volume: 319
Issue: 6056
Pages: 774-776
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/319774a0
OpenAlex: W2025801062
Cited by: 3,640
References: 19
Citations by year: 2026: 25 · 2025: 30 · 2024: 44 · 2023: 31 · 2022: 42 · 2021: 63 · 2020: 52 · 2019: 65 · 2018: 83 · 2017: 85 · 2016: 82 · 2015: 89 · 2014: 103 · 2013: 98 · 2012: 101
FWCI: 31.77
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: NMDA receptor, AP5, long-term potentiation, hippocampus, place learning, spatial learning, visual discrimination learning, glutamate receptors, intraventricular infusion, synaptic plasticity
MeSH terms: Animals, Electric Stimulation, Hippocampus, Isomerism, Learning, Valine, Visual Perception, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Receptors, Neurotransmitter, Rats

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Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5

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