Original ArticleSerotonin: its place today in sleep preparation, triggering or maintenance
Section snippets
First implication of serotonin in the sleep field
Serotonin or 5-hydroxytryptamine (5-HT) entered the sleep field by way of the seminal work of Brodie and coworkers in 1955 suggesting that reserpine was able to produce a depletion of serotonin together with sedation or a “sleep like state” [1]. Although such an approach faced a mountain of unknowns, for the first time, it formulated a possible link between serotonin and sleep and attracted the attention of hypnologists. The topography of brain monoamines, notably that of serotonin-containing
Brain anatomical substrate for serotonin
When the study of the brain substrate for serotonin began, only acetylcholine was considered as a true central neurotransmitter, its topography being known by way of cholinesterase histochemistry. In 1964, Dahlström and Fuxe [8] determined the first brain localization of serotonin-containing neurons using histofluorescence [9]. This was a real revolution in the study of monoamines in the central nervous system (CNS). Besides the technique of histofluorescence, immunohistochemical methods using
Electrolytic lesion of the raphe nuclei
Since the 5-HT component of the raphe system exhibits a limited dispersion, it was quite easy to achieve its electrolytic destruction. When the lesion of the rostral part of this system (ponto-mesencephalic subdivision) was achieved in the cat, a significant insomnia took place (duration 10–15 days) [11]. It was then possible to establish correlations between the insomnia intensity, the volume of the lesion achieved and the telencephalic 5-HT concentration that remained 10 days after lesion.
Cooling of the nucleus raphe dorsalis induces SWS and PS in the cat
In the “semi-chronic” animal preparation (head restrained; brachial plexuses cut; spinal cord transected at T4; constant infusion of procaïne at the surgical sites; patenteral feeding) [18], [19] all states of sleep (SWS and PS) occurred spontaneously after surgical recovery. Moreover, in light of the 5-HT sleep theory, localized moderate cooling (+10 °C) of the nRD, an area containing the great majority of the 5-HT perikarya, was expected to induce wakefulness, since its cooling could block
Detection of 5-OHle compounds during the sleep-wake states in the nRD
In the nRD, a structure rich in 5-HT cell bodies and dendrites [10], the 5-OHle signal exhibits variations opposite to those observed in the areas receiving 5-HT axonal nerve endings, ie, an increase during SWS and PS, compared to the waking state (Fig. 4b, c) [27], [28], [31], [32], [33]. Such variations take place particularly within the nRD clusters of serotoninergic perikarya located in the anterior part of the nucleus. They could reflect the existence of a dendritic 5-HT release occurring
Conclusions
According to the data reported and discussed here it appears that serotonin could be involved in sleep processes in two different ways: (1) when released by the axonal nerve endings during the waking state, it influences the synthesis of hypnogenic substances in specific brain targets; (2) when released by dendrites under the triggering influence of hypnogenic substances, it then contributes to the silencing of the 5-HT perikarya through an auto-inhibitory process. It is likely that NO,
Funding sources
Writing of this chapter did not receive any specific grant from funding agencies in the public, commercial, or profit sectors.
Acknowledgements
I would like to thank Pr. Michel Jouvet for his constant help regarding the research conducted on the role played by serotonin in sleep. This research started when serotonin was suggested to be the brain somnotonin. However, the first experiments that I performed in using brain localized cooling were not in favor of such a role. After 30 years of research, it appears that serotonin is involved in sleep in a complex way that concerns sleep preparation, triggering and maintenance. I am also
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