Agomelatine treatment corrects symptoms of depression and anxiety by restoring the disrupted melatonin circadian rhythms of rats exposed to chronic constant light
Abstract
Desynchronization of circadian rhythms is a hallmark of depression. The antidepressant agomelatine, which is an MT 1/MT 2 melatonin receptor agonist/5-HT 2C serotonin receptor antagonist has advantages compared to the selective serotonin reuptake inhibitors as a circadian phase-shifting agent. The present study was designed to explore whether agomelatine is able to have an antidepressant effect on rats exposed to chronic constant light (CCL) for 6 weeks. Focus is also placed on whether this activity affects diurnal rhythms of depressive-like symptoms and is associated with restoration of impaired circadian rhythms in plasma melatonin and corticosterone. We report that CCL induced a depressive-like symptoms associated with decreased grooming in the splash test during the subjective light/inactive phase. Anhedonia-like deficit in the saccharine preference test and increased immobility in the forced swimming test were both detected during the subjective dark/active phase. The disturbed emotional fluctuations due to CCL were corrected by agomelatine treatment (40 mg/kg, i.p. for 3 weeks). Agomelatine also restored novelty-induced hypophagia, which reflects an anxiety state, during the subjective Light and Dark phase, respectively, in rats exposed to CCL. Parallel to the observed positive influence on behavior, this melatonin analogue restored impaired circadian patterns of plasma melatonin but not that of corticosterone. These findings demonstrated the antidepressant-like effect of agomelatine in rats exposed to CCL possibly exerted via correction of melatonin rhythms and are suggestive of the therapeutic potential of this drug in a subpopulation of people characterized by a melatonin deficit.
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Administration of agomelatine to rats exposed to 3 and 6 weeks of constant light prevented the increase in depressive-like behavior and restored diurnal corticosterone and melatonin rhythms, respectively.
“Administration of agomelatine to rats exposed to 3 and 6 weeks of constant light prevented the increase in depressive-like behavior and restored diurnal corticosterone and melatonin rhythms respectively93,94.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [93]
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Circadian rhythm disruption and mental health
Walker, W. H., Walton, J. C., DeVries, A. C., & Nelson, R. J. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0694-0 · Cited by 1,030 · see citing works
- Authors
- Tchekalarova, J., Stoynova, T., Ilieva, K., Mitreva, R., & Atanasova, M.
- Affiliations
- Bulgarian Academy of Sciences (BG)
- Medical University Pleven (BG)
- Corresponding author
- Tchekalarova, Jana
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 171
- Pages
- 1-9
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2804295521
- Cited by
- 67
- References
- 64
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 4 · 2023: 9 · 2022: 11 · 2021: 12 · 2020: 8 · 2019: 9 · 2018: 1
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Fund of Bulgaria (03/10, 11/4)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- agomelatine, depression, anxiety, melatonin, circadian rhythm, antidepressant effects, melatonin receptor agonists, circadian phase shifting, corticosterone, anhedonia, novelty-induced hypophagia
- MeSH terms
- Acetamides, Animals, Anxiety, Behavior, Animal, Circadian Rhythm, Corticosterone, Depression, Lighting, Male, Melatonin, Naphthalenes, Rats, Sleep Phase Chronotherapy
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