Fluoxetine Modulates the Circadian Biological Clock via Phase Advances of Suprachiasmatic Nucleus Neuronal Firing
Abstract
Background The documented ability of serotonin (5-HT) to directly modulate circadian rhythms prompted interest in a similar role for therapeutic agents that readily enhance 5-HT neurotransmission, namely the selective serotonin reuptake inhibitors (SSRIs).Methods Extracellular recordings of unit firing of suprachiasmatic nucleus (SCN) neurons maintained in slice culture enabled determinations of circadian rhythmicity. Shifts in the peak of activity were determined during the next circadian cycle following drug exposure.Results Fluoxetine (10 microm, 60 minutes incubation) produced robust phase advances only in the presence of L-tryptophan (.5 microm), added to maintain serotonergic tone.Conclusions Actions of SSRIs at the level of the circadian biological clock add to the list of pharmacological effects for this drug class and encourage speculation as to their importance clinically.
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Antidepressant and mood-stabilizing medications, such as lithium, valproic acid and SSRIs, all have dramatic effects on gene expression rhythms that may, at least in part, underlie their therapeutic efficacy.
“antidepressant and mood-stabilizing medications, such as lithium, valproic acid and selective serotonin reuptake inhibitors (SSRIs), all have dramatic effects on gene expression rhythms that may, at least in part, underlie their therapeutic efficacy215–217”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [217]
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 [217]
Fluoxetine affects circadian output by producing a phase advance in the firing of SCN neurons in rat slice culture.
“Similar to morning bright light therapy, the antidepressant, fluoxetine, also affects circadian output by producing a phase advance in the firing of SCN neurons in rat slice culture (Sprouse et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Sprouse et al., 2006
The opposing therapeutic actions of SSRIs and mood stabilizers in bipolar patients could be linked to their opposing actions on rhythms, since SSRIs cause a phase advance in rhythms while lithium can cause a phase delay.
“This could be linked to their opposing actions on rhythms since SSRIs cause a phase advance in rhythms while lithium can cause a phase delay (Campbell et al., 1989; Sprouse et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Sprouse et al., 2006
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- Authors
- Sprouse, J., Braselton, J., & Reynolds, L.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Sprouse, Jeffrey
- ORCID
- Sprouse, Jeffrey
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 60
- Issue
- 8
- Pages
- 896-899
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2068814879
- Cited by
- 122
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 9 · 2012: 13
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (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
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- fluoxetine, circadian rhythm, suprachiasmatic nucleus, phase advance, selective serotonin reuptake inhibitors, serotonin, tryptophan, neuronal firing
- MeSH terms
- Animals, Circadian Rhythm, Electric Stimulation, Electrophysiology, Fluoxetine, Male, Neurons, Serotonin, Suprachiasmatic Nucleus, Tryptophan, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Rats
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