Agomelatine treatment corrects symptoms of depression and anxiety by restoring the disrupted melatonin circadian rhythms of rats exposed to chronic constant light

May 29, 2018Pharmacology, biochemistry, and behavior

Agomelatine may improve depression and anxiety by fixing disrupted daily melatonin rhythms in rats exposed to constant light

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Abstract

Agomelatine treatment (40 mg/kg) corrected depressive-like symptoms in rats exposed to chronic constant light.

Chronic constant light exposure led to decreased grooming, anhedonia, and increased immobility, indicating depressive-like symptoms.
Agomelatine treatment reduced the emotional disturbances caused by chronic constant light exposure.
The treatment restored normal patterns of plasma melatonin but did not affect corticosterone levels.
Behavioral improvements were observed during both subjective light and dark phases after agomelatine treatment.
These findings suggest that agomelatine may be effective for individuals with melatonin deficits.

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Desynchronization of circadian rhythms is a hallmark of depression. The antidepressant agomelatine, which is an MT/MTmelatonin receptor agonist/5-HTserotonin 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. 1 2 2C

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Agomelatine treatment corrects symptoms of depression and anxiety by restoring the disrupted melatonin circadian rhythms of rats exposed to chronic constant light

Abstract

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