Spike-Wave Discharges and Sleep-Wake States during Circadian Desynchronization: No Effects of Agomelatine upon Re-Entrainment

Rapid changes in the light-dark cycle cause circadian desynchronization between rhythms of spike-wave discharges (SWDs) and motor activity in genetic epileptic rats, and this is accompanied by an increase in epileptic activity. Given the close relationship between absence seizures and sleep-wake states, the present study assessed firstly a putative relationship between vigilance rhythms and SWDs during re-synchronization, and secondly sleep-wake patterns responsible for increased epileptic activity. Lastly, in a view of existing evidence that melatonin and its agonists accelerate re-synchronization, the effects of different doses of agomelatine upon the speed of re-synchronization of different sleep-wake states and SWDs were investigated. Simultaneous electroencephalographic and electromyographic recordings were made in symptomatic WAG/Rij rats, before, during and 10 days following an 8 h light phase delay. Agomelatine was orally administered acutely and sub-chronically, during 10 post-shift days. The magnitude of the advance after the shift and the speed of re-synchronization were specific for various rhythms. Most prominent change was the increase in REM sleep duration during the dark phase. A post-shift increase in passive wakefulness and a reduction in deep slow-wave sleep coincided with an aggravation of SWDs during the light phase. Agomelatine showed neither an effect on sleep-wake parameters and SWDs, nor affected re-synchronization. The same speed of re-synchronization of SWDs and light slow-wave sleep suggests that both are controlled by a common circadian mechanism. The redistribution of SWDs and their increase in the light phase after the shift may be of importance for patients with absence epilepsy planning long trans-meridian flight across time zones.