Dopamine and Memory: Modulation of the Persistence of Memory for Novel Hippocampal NMDA Receptor-Dependent Paired Associates
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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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Blockade of D1/D5 dopaminergic receptors during spatial learning impairs memory persistence.
“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]
Pharmacological studies have implicated the neurotransmitter dopamine in the stability of hippocampus-dependent memory.
“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]
Hippocampal dopaminergic activity influences long-term but not short-term memory retention in appetitive tasks.
“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
This one-trial memory for novel associations is critically dependent on the hippocampus and on glutamatergic neurotransmission during encoding.
“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]
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.
“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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“In compliance with its importance for hippocampal-dependent memory performances (Bethus et al., 2010; Broussard et al., 2016; Lisman and Grace, 2005; McNamara et al., 2014; Rosen et al., 2015; Rossato et al., 2009; Yang et al., 2017), it was not surprising that multiple studies established an early…”
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- 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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