In Vivo Resetting of the Hamster Circadian Clock by 5-HT7Receptors in the Suprachiasmatic Nucleus
Open accessAbstract
Serotonin (5-HT) has been strongly implicated in the regulation of the mammalian circadian clock located in the suprachiasmatic nuclei (SCN); however, its role in behavioral (nonphotic) circadian phase resetting remains elusive. Central to this issue are divergent lines of evidence that the SCN may, or may not, be a target for the phase-resetting effects of 5-HT. We have addressed this question using a novel reverse-microdialysis approach for timed perfusions of serotonergic and other agents to the Syrian hamster SCN with durations equivalent to the increases in in vivo 5-HT release during phase-resetting behavioral manipulations. We found that 3 hr perfusions of the SCN with either 5-HT or the 5-HT(1A,7) receptor agonist 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydro-naphthalene (8-OH-DPAT) at midday advanced the phase of the free-running circadian rhythm of wheel-running assessed using an Aschoff type II procedure. Phase shifts induced by 8-OH-DPAT were enhanced more than threefold by pretreatment with the 5-HT synthesis inhibitor para-chlorophenylalanine. Phase advances induced by SCN 8-OH-DPAT perfusion were significantly inhibited by the 5-HT(2,7) receptor antagonist ritanserin and by the more selective 5-HT(7) receptor antagonist DR4004, implicating the 5-HT(7) receptor in mediating this phase resetting. Concurrent exposure to light during the 8-OH-DPAT perfusion abolished the phase advances. Furthermore, coperfusion of the SCN with TTX, which blocked in vivo 5-HT release, did not suppress intra-SCN 8-OH-DPAT-induced phase advances. These results indicate that 5-HT(7) receptor-mediated phase resetting in the SCN is markedly influenced by the degree of postsynaptic responsiveness to 5-HT and by photic stimulation. Finally, 5-HT may act directly on SCN clock cells to induce in vivo nonphotic phase resetting.
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In adult rodents, activation of serotonin receptors, either the 5-HT1A, 5-HT2, or 5-HT7 receptor subtypes, resets the phase of the suprachiasmatic nucleus circadian pacemaker.
“In adult rodents, activation of serotonin receptors, either the 5-HT1A, 5-HT2, or 5-HT7 receptor subtypes, resets the phase of the SCN circadian pacemaker (Tominaga et al., 1992; Gannon and Millan 2006; Ehlen et al., 2001; Duncan et al., 2004)”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Ehlen et al., 2001
Serotonin neurons from the midbrain raphe nuclei innervate the SCN, and local applications of 5-HT or 5-HT1A and 7 receptor agonists to the SCN produce a phase advance in circadian activity.
“Indeed, serotonin neurons from the midbrain raphe nuclei innervate the SCN, and local applications of 5-HT or 5-HT 1A and 7 receptor agonists to the SCN will also produce a phase advance in circadian activity (Dudley et al., 1999; Ehlen et al., 2001).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Ehlen et al., 2001
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References 57 · Cited by 139
Research works printed but not linked: 1
- Klein DC, Moore RM, Reppert SM (1991) Suprachiasmatic nucleus: the minds clock. New York: Oxford UP.
- Authors
- Ehlen, J. C., Grossman, G. H., & Glass, J. D.
- Affiliations
- Kent State University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-07-15
- Volume
- 21
- Issue
- 14
- Pages
- 5351-5357
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762851
- OpenAlex
- W2102660603
- Cited by
- 139
- References
- 57
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 7
- FWCI
- 3.92
- 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
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS35229, R01NS035229)
- 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 › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- circadian clock, phase resetting, 5-HT7 receptor, serotonin, suprachiasmatic nucleus, non-photic entrainment, 8-OH-DPAT, ritanserin, p-chlorophenylalanine, tetrodotoxin, light entrainment, golden hamster
- MeSH terms
- Animals, Biological Clocks, Chromatography, High Pressure Liquid, Circadian Rhythm, Cricetinae, Injections, Subcutaneous, Light, Male, Mesocricetus, Motor Activity, Fenclonine, Perfusion, Photic Stimulation, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Suprachiasmatic Nucleus, Tetrodotoxin, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Microdialysis
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