engleski

The role of 5-HT receptors in sleep

For the last 50 years, since time of its isolation from the platelets and intestinal mucosa, 5-hydroxytryptamine (5-HT, serotonin) has been in the center of the research. Althought isolation and purification of serotonin were based on studies of blood pressure regulation, the possible relation of serotonin to psychiatric disorders propelled research to the central effects of serotonin. Serotonergic neurotransmission plays an important role in modulation of the behavioural state by interacting with other brain areas modulating circadian rhythm, sleep and waking. Serotonin was first believed to be a true neuromodulator of sleep because the destruction of 5-HT neurons of the raphe system or the inhibition of 5-HT synthesis with p-chlorophenylalanine induced a severe insomnia, which could be reversed by restoring 5-HT synthesis. On the other hand, electrical activity of 5-HT perikarya and the release of 5-HT are increased during waking and decreased during sleep, which is in contradiction to the early studies. More recent studies suggest that the release of 5-HT during waking may initiate a cascade of genomic events in some neurons located in preoptic area. This may lead to a progressive synthesis of sleep factors in preoptic area to induce sleep. Also, several findings have strengthened the case of possible influence of serotonin in sleep inducing processes. Some serotonergic neurons fire maximally during the slow wave sleep, pharmacologically induced silence of dorsal raphe nucleus induces waking, and inhibition of 5-HT neurons of dorsal raphe nucleus by acting on 5-HT1A receptors increases paradoxical sleep. Further research into the very many 5-HT receptors should answer important questions about the type of 5-HT receptors and the area of the brain (eg. preoptic area and dorsal raphe) involved in the regulation of sleep and wake cycles.

serotonin; sleep; raphe nuclei

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