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Dopamine and Memory: Modulation of the Persistence of Memory for Novel Hippocampal NMDA Receptor-Dependent Paired Associates
Open accessAbstract
Three experiments investigated the role in memory processing of dopamine (DA) afferents to the hippocampus (HPC) that arise from the ventral tegmental area. One hypothesis is that D 1 /D 5 receptor activation in HPC is necessary for the encoding of novel, episodic-like information; the other is that DA activation ensures the greater temporal persistence of transient hippocampal memory traces. Rats ( n = 35) were trained, in separate experiments using an episodic-like memory task, to learn six paired associates (PAs) in an “event arena” involving a repeated association between specific flavors of food and locations in space. After 6 weeks of training, rats had learned a “schema” such that two new paired associates could be acquired in a single trial in one session (episodic-like memory). We show that encoding of novel PAs is sensitive to intrahippocampal microinfusion of the NMDA antagonist d -AP-5. Experiment 1 established that intrahippocampal infusion of the D 1 /D 5 dopaminergic antagonist SCH23390 [ R (+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H -3-benzazepine hydrochloride] before encoding of new PAs caused impaired memory 24 h later but that SCH23390 had no effect on the later memory of previously established PAs. Experiment 2 established that SCH23390 modulated the persistence of new memories over time (30 min vs 24 h) rather than affecting initial encoding. Experiment 3 revealed that the impact of SCH23390 was not mediated by state dependence nor had an effect on memory retrieval. These findings support the second hypothesis and establish that persistent, long-term memory of rapid, hippocampal-mediated acquisition of new paired associates requires activation of D 1 /D 5 receptors in HPC at or around the time of encoding.
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In the citing paper
“Blockade of D1/D5 dopaminergic receptors during spatial learning impairs memory persistence7”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [7]
In the citing paper
“Pharmacological studies have implicated the neurotransmitter dopamine in the stability of hippocampus-dependent memory.”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [7]
In the citing paper
“hippocampal dopaminergic activity was shown to influence long-term but not short-term memory retention in appetitive tasks (Bethus et al., 2010).”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Bethus et al., 2010
In the citing paper
“This one-trial memory for novel associations is critically dependent on the hippocampus and on glutamatergic neurotransmission during encoding [25, 26].”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [26]
In the citing paper
“Intrahippocampal infusion of the D1/D5 dopaminergic antagonist SCH23390 just before encoding causes impaired memory for the new reward-location association measured 24 hours later, but has no effect on early memory measured at 30 minutes [26]”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [26]
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Metadata
- Authors
- Bethus, I., Tse, D., & Morris, R. G. M.
- Affiliations
- University of Edinburgh (GB)
- Corresponding author
- Bethus, Ingrid
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-02-03
- Volume
- 30
- Issue
- 5
- Pages
- 1610-1618
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6633999
- OpenAlex
- W2168456060
- Cited by
- 270
- References
- 57
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 12 · 2023: 8 · 2022: 19 · 2021: 17 · 2020: 12 · 2019: 13 · 2018: 17 · 2017: 22 · 2016: 26 · 2015: 25 · 2014: 16 · 2013: 18 · 2012: 21
- FWCI
- 12.03
- 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)
- Edge Hill University Research Information Repository (Edge Hill University) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Medical Research Council
- 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 › Memory Processes and Influences
- Keywords
- dopamine, hippocampus, paired associates, episodic-like memory, memory persistence, NMDA receptor antagonism, SCH 23390, ventral tegmental area, memory encoding, state dependence, memory retrieval
- MeSH terms
- Analysis of Variance, Animals, Benzazepines, Cues, Dopamine, Hippocampus, Male, Memory, Memory, Short-Term, Reaction Time, Retention, Psychology, Receptors, N-Methyl-D-Aspartate, Receptors, Dopamine D1, Rats
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