BACKGROUND AND AIMS: Spontaneous, rhythmic occurrence of absence seizures in WAG/Rij rats, a validated animal model of childhood absence epilepsy, is determined by the circadian timing system. Stable phase-relationship between seizures and sleepwake states is maintained in the 12:12 light-dark cycle. In man, rapid changes in the photoperiod, e.g. caused by long-distance air travels, result in loss of the synchrony. Melatonin and its agonists were found to accelerate re-synchronization. The aims of the present study were to investigate in WAG/Rij rats the re-adaptation of the various sleep-wake states and absence seizures to an 8 h phase delay and to assess the effect of the melatonergic antidepressant agomelatine on the speed of re-synchronization of the different electroencephalographic (EEG) states. METHODS: Simultaneous EEG and electromyographic (EMG) recordings were made in adult, male rats to assess the effect of various doses of agomelatine on sleep-wake states and absence seizures (acute study, 3 days) and to investigate the effect of the compound on the process of re-synchronization after the phase delay (chronic study, 11 days). RESULTS: Agomelatine showed neither an effect on sleep-wake parameters in the acute study, nor affected the SWDs and the resynchronization process in the chronic study. Internal desynchronization between various rhythms was observed, however, some rhythms remained coupled (active wakefulness and deep slowwave sleep, SWDs and light slow-wave sleep). A post-shift increase in passive wakefulness and a reduction in deep slow-wave sleep resulted in an aggravation of epileptic activity (light phase). CONCLUSIONS: Different speed of re-entrainment and coupling between various rhythms suggests that SWDs and light slow-wave sleep are controlled by common circadian mechanism distinct from that for active wakefulness and deep slow-wave sleep. The increase in the number of seizures after the phase shift may be of significant importance for people with epilepsy planning a transmeridian flight.
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