Electroencephalographic study of the effects of methysergide on sleep in the rabbit

The effects of methysergide, a serotonin (5-HT) blocking agent, on the sleep-wakefulness cycle were studied in nine male rabbits with chronically implanted electrodes for the EEG, the EMG of the neck muscles and the oculogram. Methysergide (1.0 and 4.0 mg/kg) markedly delayed the occurrence of the first episode of paradoxical sleep, increased the percent time of the alert stage and decreased that of slow wave and of paradoxical sleep in the 6 h recordings made immediately after the injections. These effects of methysergide were more marked on paradoxical sleep than on slow wave sleep. Prolonged observations following single injections of 4.0 mg/kg of methysergide demonstrated not only a decrease in paradoxical sleep but also a tendency to a rebound on the 3rd day with return toward normal levels on the 4th day. With chronic administration of 1.0 mg/kg of methysergide 4 days in succession, clear decreases in both phases of sleep were observed only on the 1st day. On drug withdrawal, a marked rebound of paradoxical sleep occurred. We consider that these effects, decreases in both phases of sleep, were caused by the 5-HT blocking action of methysergide in the brain. The present results provide additional support for the hypothesis that 5-HT plays an important role in the production of sleep. However, our results also indicate that in the rabbit, the role of 5-HT is more important in paradoxical sleep than in slow wave sleep. Les effets du méthysergide, produit bloquant le sérotonine (5-HT), sur le cycle veille-sommeil ont été étudiés sur neuf lapins mâles avec électrodes implantées chroniquement pour enregistrer l'EEG, l'EMG des muscles du cou et l'oculogramme. Le méthysergide (1.0 et 4.0 mg/kg) retarde de façon marquée la survenue du premier épisode de sommeil paradoxal, augmente le pourcentage de veille et diminue celui du sommeil lent et du sommeil paradoxal au cours des enregistrements de 6 h faits immédiatement après les injections. Ces effets du méthysergide sont plus marqués sur le sommeil paradoxal que sur le sommeil lent. Des observations prolongées après injection unique de 4 mg/kg de méthysergide montrent non seulement une diminution du sommeil paradoxal, mais également une tendance à un rebound au 3ème jour avec retour à des taux normaux lors du 4ème jour. Avec administration chronique de 1 mg/kg de méthysergide pendant 4 jours consécutifs, une nette diminution des phases de sommeil lent et paradoxal ne s'observe que le premier jour. Lors du sevra