Serotonin‐induced phase advances of SCN neuronal firing in vitro: A possible role for 5‐HT5A receptors?
Abstract
Spontaneous firing rates of neurons in the suprachiasmatic nuclei (SCN) follow a consistent pattern, peaking near the midpoint of the light phase in a 12:12 light/dark schedule, and repeating this brief period of increased activity in subsequent circadian cycles. These carefully timed fluctuations reflect the output signal of the SCN, long recognized as the site of the endogenous biological clock in mammals. In rat hypothalamic slices, bath incubations of 8‐OH‐DPAT had previously been shown to elicit phase advances when applied at ZT6 (or 6 h following the onset of light), an action that could readily be attributed to 5‐HT 7 receptor activation. The present studies set out with the simple goal of establishing that the same receptor mechanism was responsible for the phase‐shifting actions of 5‐HT itself. Surprisingly, the phase advances elicited by 5‐HT (0.5 μM, 1 h) at ZT6 were reduced by one 5‐HT 7 antagonist, ritanserin (10 μM), but not by another, mesulergine (10 μM). Receptor binding studies demonstrated a 25‐fold greater affinity of ritanserin for h5‐HT 5A sites compared to mesulergine (K i = 71 nM vs. 1,800 nM), an observation suggestive of a 5‐HT 5A mechanism for 5‐HT and consistent with earlier observations of robust labeling of 5‐HT 5A sites in the SCN. 5‐HT generated by the addition of L‐tryptophan (10 μM, 1 h) to the slices displayed the same pattern of sensitivity, that is, blockade by ritanserin but not by mesulergine. Rp‐cAMPS, a cAMP antagonist, failed to block the phase shifts elicited by 5‐HT at a concentration (1 μM) previously shown to be effective against 8‐OH‐DPAT‐induced phase shifts, in keeping with the proposed negative coupling of 5‐HT 5A receptors to cAMP production. Taken together, these results suggest that activation of both 5‐HT 5A and 5‐HT 7 receptors can produce phase advances of the circadian clock in vitro when they occur during mid‐subjective day. Synapse 54:111–118, 2004. © 2004 Wiley‐Liss, Inc.
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Targeting rhythms or components of the clock using pharmacological agents might be therapeutically beneficial.
“they suggest that targeting rhythms or components of the clock using pharmacological agents might be therapeutically beneficial215,216,331”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [331]
Several first-line pharmacological treatments for psychiatric disorders, such as lithium for bipolar disorder and SSRIs for major depressive disorders, modulate the circadian clock.
“Several first-line pharmacological treatments for psychiatric disorders, such as lithium for bipolar disorder and SSRIs for major depressive disorders, modulate the circadian clock216,217,329–331.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [331]
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Self-citation
- Authors
- Sprouse, J., Reynolds, L., Braselton, J., & Schmidt, A.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Sprouse, Jeffrey
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2004-08-16
- Volume
- 54
- Issue
- 2
- Pages
- 111-118
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- OpenAlex
- W2045856588
- Cited by
- 44
- References
- 33
- Citations by year
- 2023: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 5
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- serotonin, 5-HT5A receptor, 5-HT7 receptor, suprachiasmatic nucleus, circadian phase shift, phase advance, ritanserin, mesulergine, cAMP signaling, 8-OH-DPAT, circadian clock, hypothalamic slices, receptor binding affinity
- MeSH terms
- Action Potentials, Animals, Circadian Rhythm, Drug Interactions, Electrophysiology, Male, Neurons, Radioligand Assay, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Suprachiasmatic Nucleus, Tryptophan, Rats, Sprague-Dawley, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Rats, In Vitro Techniques
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