Effects of sertindole on sleep-wake states, electroencephalogram, behavioral patterns, and epileptic activity of rats

Abstract

In this study we addressed the effects of the 5-HT 2 receptor antagonist sertindole in rats. The compound was administered in doses of 0.08, 0.32, and 1.28 mg/kg, whereas a control group received the solvent. The effects of sertindole on sleep-wake states, behavioral patterns, and background electroencephalogram were studied. Following injection of drug or solvent, we recorded the electroencephalogram and electromyogram for two periods of 4 h in the dark period of the light-dark cycle on 2 successive days. On the 1st day sertindole induced a significant increase in deep slow-wave sleep, but only with a dose of 0.32 mg/kg. Furthermore, a decrease in REM sleep in all three drug groups was established. The suppression of REM sleep was still present on the 2nd day. Sertindole also induced a decrease in alternation between behavioral patterns on the 1st day. There were no significant changes in the spectral content of the background electroencephalogram. In a parallel experiment it appeared that sertindole had no main effects on epileptic spike-wave discharges. This was established with a dose of 1.28 mg/kg sertindole in rats with absence seizures. These findings suggest that sertindole, similar to other compounds modulating 5-HT 2 receptors, influences sleep-wake states in rats by decreasing REM sleep and mildly increasing deep slow-wave sleep, whereas behavioral variation is slightly diminished, with no effects on the background EEG and almost no effects on spike-wave discharges.