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Fluoxetine modifies circadian rhythm by reducing melatonin content in zebrafish
Mei-Li Wei1, Shi-Min He2, An-Qi Chen2
1Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resource Conservation and Bio-breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; School of Life Science, Anhui Province Key Laboratory of Translational Cancer Research, Anhui Province Key Laboratory of Immunology in Chronic Diseases, Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, Anhui Province 233030, China.
Fluoxetine (FLX) disrupts zebrafish circadian rhythm by altering clock gene expression and melatonin production. This selective serotonin reuptake inhibitor (SSRI) impacts locomotor activity and internal biological timing.
Area of Science:
- Neuroscience
- Chronobiology
- Pharmacology
Background:
- Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (FLX) are used to treat depression by increasing brain serotonin.
- Antidepressants are known to influence circadian rhythms, but the precise mechanisms remain unclear.
- Understanding how FLX affects biological timing is crucial for its clinical application.
Purpose of the Study:
- To investigate the effects of fluoxetine (FLX) on circadian rhythm and locomotor activity in zebrafish.
- To elucidate the molecular mechanisms underlying FLX's impact on internal circadian oscillations.
Main Methods:
- Zebrafish were treated with FLX to analyze changes in movement behavior.
- Expression levels of key clock genes (clock1a, bmal1b) and aanat2 were quantified.
- Melatonin secretion was assessed, and aanat2 knockout zebrafish were used to study circadian disruption.
Main Results:
- FLX treatment significantly down-regulated clock1a and bmal1b gene expression in zebrafish.
- FLX exposure led to reduced amplitude and phase shifts in circadian oscillations.
- Inhibition of aanat2 expression by FLX decreased nocturnal melatonin secretion, and aanat2 knockout larvae exhibited disrupted circadian rhythms.
Conclusions:
- Fluoxetine (FLX) significantly impacts the circadian rhythm and locomotor activity in zebrafish.
- FLX disrupts the expression of core clock genes and melatonin synthesis pathway.
- These findings provide insights into the effects of SSRIs on biological timing and may inform clinical use.
