Comparison of the Effect of the Antidepressants Imipramine and Fluoxetine on the Sleep–Wake Cycle and Characteristics of Sleep Spindles in Wag/Rij Rats with Absence Epilepsy and Comorbid Depression

WAG/Rij rats are a valid model of absence epilepsy and comorbiddepression. We have previously shown that WAG/Rij rats have disturbancesin the sleep–wake cycle and changes in the characteristics of sleepspindles. A negative correlation was also found between the numberof spike-wave discharges (SWD) and the duration of rapid eye movement(REM) sleep. Clinical evidence suggests that the traditional antidepressantsimipramine and fluoxetine are effective in suppressing symptomsof depression, but may have a negative impact on the sleep–wakecycle and comorbid epilepsy in patients. Our previous studies inWAG/Rij rats showed that imipramine, when administered chronically, increasesthe number of SWDs, while fluoxetine at the same dose reduces theirnumber, although both antidepressants have a pronounced antidepressanteffect. Comparison of the effects of the antidepressants imipramineand fluoxetine on the sleep–wake cycle and sleep spindles in WAG/Rijrats remains unstudied. The purpose of this work is to find out:(1) what effects do imipramine and fluoxetine have on the sleep–wakecycle and the characteristics of sleep spindles in WAG/Rij ratsand (2) whether there are differences in their effects. To achievethis goal, the characteristics of the sleep–wake cycle and sleepspindles were compared in WAG/Rij rats after chronic administrationof antidepressants and saline and in non-epileptic Wistar rats.Administration of imipramine led to a significant decrease in the durationof REM sleep. The administration of imipramine, compared with fluoxetine,also increased the latency of the transition to sleep and the transitionto REM sleep. Sleep spindle amplitude was significantly increasedby both antidepressants. However, the spectral power density of“slow” and “medium” spindles, which predominate in WAG/Rij ratscompared to Wistar rats, was significantly higher after administrationof imipramine than fluoxetine. The results suggest that imipraminecauses greater negative changes in the sleep–wake cycle and sleepspindles than fluoxetine. Studies in the WAG/Rij rat model indicatethat fluoxetine is more preferable antidepressant for the treatmentof depressive disorders comorbid with absence epilepsy, since itdoes not cause a significant deterioration in sleep quality. Theseresults are consistent with clinical data.