D1/D5 dopamine receptor activation increases the magnitude of early long-term potentiation at CA1 hippocampal synapses
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The role of the mesolimbic dopaminergic system in the reinforcement of learning suggests that dopamine should be able to modulate activity-dependent synaptic plasticity. We have examined the effect of D1/D5 agonists on early long-term potentiation (LTP) (40 min) in the CA1 region of hippocampal slices. D1/D5 agonists (+)bromo-APB, 6-chloro-PB, and dihydrexidine increased the magnitude of LTP in a synapse-specific manner (by approximately 10, 15, and 20%, respectively). This D1/D5 effect was mimicked by a low dose (10 microM) of the adenylyl cyclase activator forskolin. The D1/D5 antagonist (+)SCH 23390 reduced early LTP. In catecholamine-depleted slices, LTP was smaller by approximately 20-25% and could not be decreased further by D1/D5 antagonist. Under these conditions, D1/D5 agonist 6-chloro-PB and forskolin produced a larger enhancement of LTP (20-25%), restoring it to the control level. At the same dose, dideoxyforskolin did not affect early LTP. The D1/D5 agonist effect was completely blocked by the D1/D5 antagonist (+)SCH 23390. These results indicate that dopamine produces a synapse-specific enhancement of early LTP through D1/D5 receptors and cAMP.
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With less strong induction protocols, there is a partial inhibition of early LTP.
“Subsequent work, however, showed that, with less strong induction protocols, there is a partial inhibition of early LTP [23].”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [23]
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- Authors
- Otmakhova, N. A., & Lisman, J. E.
- Affiliations
- Brandeis University (US)
- ORCID
- Lisman, John E.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-12-01
- Volume
- 16
- Issue
- 23
- Pages
- 7478-7486
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6579102
- OpenAlex
- W1868297237
- Cited by
- 377
- References
- 72
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 13 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 2 · 2019: 7 · 2018: 15 · 2017: 15 · 2016: 12 · 2015: 18 · 2014: 23 · 2013: 14 · 2012: 27
- FWCI
- 3.37
- 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)
- Funders
- W. M. Keck Foundation
- Abbott Laboratories
- National Institutes of Health
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke (R01NS027337, 5 R01 NS27337-7)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dopamine D1/D5 receptors, long-term potentiation, hippocampal CA1, synaptic plasticity, adenylate cyclase, cAMP signaling, forskolin, SCH 23390, catecholamine depletion, learning reinforcement, mesolimbic dopamine system
- MeSH terms
- Animals, Catecholamines, Colforsin, Hippocampus, Rats, Inbred Strains, Synapses, Receptors, Dopamine D1, Long-Term Potentiation, Dopamine Agonists, Dopamine Antagonists, Receptors, Dopamine D5, Rats
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