Biogenic Amines and the States of Sleep
Michel Jouvet
Science 163 (862) pages : 32-41 (1969)


The Four Major Concepts

Biogenic Amines and the Sleep States

Insomnia Following Selective Decrease of Cerebral Serotonin

The Problem of Paradoxical Sleep



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Recent advances in the physiology of sleep have led to the understanding that sleep is comprised of two succes sive functional states (slow-wave sleep and paradoxical sleep) which depend upon active mechanisms. These two states can be accurately quantified, and selectively modified or suppressed by either specific drugs or limited les ions.

The hypothesis that cerebral serotonin has a role in the process of sleep is strongly supported by two series of experiments. (i) Inhibition of the synthesis of serotonin at the level of tryptophan hydroxylase by p-chlorophenylalanine leads to total insomnia which is reversible; return to normal sleep is effected by the injection of 5-hydroxytryptophan, the immediate precursor of serotonin. (ii) Total destruction of serotonin-containing neurons located in the raphe system (as determined by histofluorescence ) also leads to total insomnia. A three-way correlation exists between the extent of destruction of the raphe, the decrease in cerebral serotonin, and the resulting insomnia.

Paradoxical sleep appears to depend upon "priming" serotonergic mecha nisms located in the caudal raphe system and upon "triggering" mechanisms located in the nuclei of the locus coeruleus. Destruction of these nuclei leads to the suppression of paradoxical sleep without alteration of slow-wave sleep. The successive intervention of serotonergic, cholinergic, and noradrenergic mechanisms in the triggering and effecting of paradoxical sleep is strongly implied by neuropharmacological results.

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