Jana Tchekalarova1, Lidia Kortenska2, Natasha Ivanova2, Milena Atanasova3, Pencho Marinov4. 1. Institute of Neurobiology, Bulgarian Academy of Sciences (BAS), 1113, Sofia, Bulgaria. janetchekalarova@gmail.com. 2. Institute of Neurobiology, Bulgarian Academy of Sciences (BAS), 1113, Sofia, Bulgaria. 3. Department of Biology, Medical University of Pleven, 5800, Pleven, Bulgaria. 4. Institute of Information and Communication Technologies, BAS, 1113, Sofia, Bulgaria.
Abstract
RATIONALE: Exposure to chronic constant light (CCL) has a detrimental impact on circadian rhythms of motor activity and sleep/wake cycles. Agomelatine is an atypical antidepressant showing a chronotropic activity. OBJECTIVES: In this study, we explored the role of melatonin (MT) receptors and brain-derived neurotrophic factor (BDNF) in the brain in the mechanism underlying the effects of agomelatine on diurnal variations of motor activity, sleep/wake cycle, and sleep architecture in a rat model of CCL. METHODS: In Experiment #1, home cage activity was monitored automatically with cameras for a period of 24 h. The diurnal rhythm of MT1, MT2 receptors, and BDNF expression in the hippocampus and frontal cortex (FC), was tested using the ELISA test. In Experiment #2, rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and recordings were made under basal conditions (12:12 LD cycle + vehicle), LL + vehicle and LL + agomelatine (40 mg/kg/day for 21 days). RESULTS: The rats exposed to CCL showed an impaired diurnal rhythm of motor activity and sleep/wake cycle with reduced NREM sleep and delta power and increased REM sleep and theta power. The duration and number of episodes of the wake were diminished during the subjective dark phase in this group. The circadian rhythm of MT1 and MT2 receptors and their expression did not change in the hippocampus and FC under CCL exposure, while the BDNF levels in the hippocampus decreased during the subjective light phase. Agomelatine restored the diurnal rhythm of motor activity, disturbed sleep/wake cycle, and sleep architecture, which effect was accompanied by an increase in MT1 receptor and BDNF expression in the hippocampus at 10:00 in CCL rats. CONCLUSIONS: These findings support the value of agomelatine as an antidepressant that can adjust circadian homeostasis of motor activity and sleep/wake cycle in a CCL model.
RATIONALE: Exposure to chronic constant light (CCL) has a detrimental impact on circadian rhythms of motor activity and sleep/wake cycles. Agomelatine is an atypical antidepressant showing a chronotropic activity. OBJECTIVES: In this study, we explored the role of melatonin (MT) receptors and brain-derived neurotrophic factor (BDNF) in the brain in the mechanism underlying the effects of agomelatine on diurnal variations of motor activity, sleep/wake cycle, and sleep architecture in a rat model of CCL. METHODS: In Experiment #1, home cage activity was monitored automatically with cameras for a period of 24 h. The diurnal rhythm of MT1, MT2 receptors, and BDNF expression in the hippocampus and frontal cortex (FC), was tested using the ELISA test. In Experiment #2, rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and recordings were made under basal conditions (12:12 LD cycle + vehicle), LL + vehicle and LL + agomelatine (40 mg/kg/day for 21 days). RESULTS: The rats exposed to CCL showed an impaired diurnal rhythm of motor activity and sleep/wake cycle with reduced NREM sleep and delta power and increased REM sleep and theta power. The duration and number of episodes of the wake were diminished during the subjective dark phase in this group. The circadian rhythm of MT1 and MT2 receptors and their expression did not change in the hippocampus and FC under CCL exposure, while the BDNF levels in the hippocampus decreased during the subjective light phase. Agomelatine restored the diurnal rhythm of motor activity, disturbed sleep/wake cycle, and sleep architecture, which effect was accompanied by an increase in MT1 receptor and BDNF expression in the hippocampus at 10:00 in CCL rats. CONCLUSIONS: These findings support the value of agomelatine as an antidepressant that can adjust circadian homeostasis of motor activity and sleep/wake cycle in a CCL model.
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