Molecular mechanism regulating 24-hour rhythm of dopamine D3 receptor expression in mouse ventral striatum
Abstract
The dopamine D3 receptor (DRD3) in the ventral striatum is thought to influence motivation and motor functions. Although the expression of DRD3 in the ventral striatum has been shown to exhibit 24-hour variations, the mechanisms underlying the variation remain obscure. Here, we demonstrated that molecular components of the circadian clock act as regulators that control the 24-hour variation in the expression of DRD3. The transcription of DRD3 was enhanced by the retinoic acid-related orphan receptor α (RORα), and its activation was inhibited by the orphan receptor REV-ERBα, an endogenous antagonist of RORα. The serum or dexamethasone-induced oscillation in the expression of DRD3 in cells was abrogated by the downregulation or overexpression of REV-ERBα, suggesting that REV-ERBα functions as a regulator of DRD3 oscillations in the cellular autonomous clock. Chromatin immunoprecipitation assays of the DRD3 promoter indicated that the binding of the REV-ERBα protein to the DRD3 promoter increased in the early dark phase. DRD3 protein expression varied with higher levels during the dark phase. Moreover, the effects of the DRD3 agonist 7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT)-induced locomotor hypoactivity were significantly increased when DRD3 proteins were abundant. These results suggest that RORα and REV-ERBα consist of a reciprocating mechanism wherein RORα upregulates the expression of DRD3, whereas REV-ERBα periodically suppresses the expression at the time of day when REV-ERBα is abundant. Our present findings revealed that a molecular link between the circadian clock and the function of DRD3 in the ventral striatum acts as a modulator of the pharmacological actions of DRD3 agonists/antagonists.
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Dopamine type 3 receptors show 24-hour fluctuations which are regulated by the canonical molecular clock.
“Dopamine type 3 receptors also show 24-h fluctuations which are regulated by the canonical molecular clock (Ikeda et al., 2013).”
From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Ikeda et al., 2013
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- Authors
- Ikeda, E., Matsunaga, N., Kakimoto, K., Hamamura, K., Hayashi, A., Koyanagi, S., & Ohdo, S.
- Affiliations
- Kyushu University (JP)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 83
- Issue
- 5
- Pages
- 959-967
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2123427001
- Cited by
- 50
- References
- 37
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 8
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23659084, 13J04175)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- dopamine D3 receptor, ventral striatum, circadian clock, RORα, NR1D1, gene expression oscillations, 7-OH-DPAT, dexamethasone, dark phase, circadian rhythm
- MeSH terms
- Animals, Basal Ganglia, Cell Line, Circadian Rhythm, Dexamethasone, Motor Activity, Promoter Regions, Genetic, RNA, Messenger, Tetrahydronaphthalenes, Transcription, Genetic, Down-Regulation, Up-Regulation, NIH 3T3 Cells, Cell Line, Tumor, Chromatin Immunoprecipitation, Receptors, Dopamine D3, Mice, Nuclear Receptor Subfamily 1, Group D, Member 1, Nuclear Receptor Subfamily 1, Group F, Member 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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