EFFECTS OF SERTINDOLE ON SLEEP-WAKE STATES, ELECTROENCEPHALOGRAM, BEHAVIORAL-PATTERNS, AND EPILEPTIC ACTIVITY OF RATS

In this study we addressed the effects of the 5-HT2 receptor antagonis t 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. Th e 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 electromyogr am for two periods of 4 h in the dark period of the light-dark cycle o n 2 successive days. On the Ist day sertindole induced a significant i ncrease in deep slow-wave sleep, but only with a dose of 0.32 mg/kg. F urthermore, a decrease in REM sleep in all three drug groups was estab lished. The suppression of REM sleep was still present on the 2nd day. Sertindole also induced a decrease in alternation between behavioral patterns on the Ist day. There were no significant changes in the spec tral content of the background electroencephalogram. In a parallel exp eriment it appeared that sertindole had no main effects on epileptic s pike-wave discharges. This was established with a dose of 1.28 mg/kg s ertindole in rats with absence seizures. These findings suggest that s ertindole, similar to other compounds modulating 5-HT2 receptors, infl uences sleep-wake states in rats by decreasing REM sleep and mildly in creasing deep slow-wave sleep, whereas behavioral variation is slightl y diminished, with no effects on the background EEG and almost no effe cts on spike-wave discharges.