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.