Discussion of Insomnia and Decrease of Cerebral 5-Hydroxytryptamine after Destruction of the Raphe System in the Cat

Abstract

Publisher Summary Experimental studies show that particular structures of the brain are necessary for normal sleep and consequently, that these structures are at least part of a sleep-controlling apparatus. 5-HT is involved in the organization and, possibly, the control of sleep, particularly of slow sleep. Methysergide, a 5-HT-blocking agent, which is frequently employed as a preventive agent for migraine, produces insomnia in a number of subjects. Cats pretreated with 0.6 mg/kg of reserpine exhibit a reduction in slow sleep for about 2 days and loss of the tonic components of paradoxical sleep for up to 4 days. Treatment with p -chlorophenylalanine drastically reduces slow as well as paradoxical sleep in cats. It takes as long as 7–8 days before the animals are recovered from the effect of this compound, which markedly depletes brain 5-HT and to a much lesser extent, catecholamines, by inhibition of the hydroxylase. Small amounts of 5-HT (threshold doses about 0.2 μg/kg) injected into the carotid artery of cats leads to initial transient depression, followed by protracted enhancement of the recruiting response for as long as 20 minutes. 5-HT also produces initial desynchronization of the spontaneous electrocorticogram followed by prolonged hypersynchrony with high voltage slow waves and appearance of, or increase in, sleep spindles.