The large night-time growth hormone (GH) pulses are associated with slow
wave sleep (SWS) phases in humans and a similar association has been found
also in some other mammalian species. According to previous pharmacological
studies an administration of growth hormone-releasing hormone (GHRH) promotes
sleep, especially SWS, in humans and laboratory animals. Similar studies
in rats have shown that somatostatin promotes REM sleep. The neuropeptide
galanin increases GH-secretion and induces sleep in humans. The cells synthetising
GHRH, somatostatin and galanin are mainly located in the hypothalamic areas.
In order to study the possible endogenous role of GHRH, somatostatin and
galanin in sleep regulation we measured the effect of REM and total sleep
deprivation on the expression of mRNA of these neuropeptides in the rat
hypothalamus by in situ hybridization. We also measured the effect of galanin,
somatostatin and somatostatin antagonist on sleep by a polygraphic method
in the course of which these peptides were injected intracerebroventricularly
(i.c.v.) or locally into the locus coeruleus of rats. We observed that
selective REM sleep deprivation increased the amount of somatostatin mRNA
in the arcuate nucleus and decreased GHRH mRNA in the paraventricular nucleus.
Combined loss of REM sleep and SWS achieved by total sleep deprivation
increased both somatostatin and GHRH mRNA in these hypothalamic nuclei.
Because the paraventricular (GHRH) and arcuate (somatostatin) nuclei are
not the main hypophysiotropic nuclei of GHRH and somatostatin, control
of sleep and wakefulness and GH regulatory functions of these neuropeptides
are presumably performed by different cell populations in the hypothalamus.
REM sleep deprivation increased the amount of galanin mRNA in the hypothalamus,
while total sleep deprivation had no effects. I.c.v. or locus coeruleus
microinjections of galanin did not have effects on sleep. These findings
suggest that galanin may mediate some effects of REM sleep deprivation
in the brain, but does not regulate REM sleep by itself. I.c.v. or local
injection of somatostatin did not affect daytime sleep in rats, but a somatostatin
antagonist reduced REM sleep when injected i.c.v. or locally into the locus
coeruleus. I.c.v. injection of somatostatin antagonist also reduced REM
sleep when REM sleep propensity was elevated after REM sleep deprivation.
The present findings support the hypothesis that endogenous GHRH promotes
SWS while somatostatin promotes REM sleep. We hypothesize that the
locus coeruleus may partly mediate the effects of somatostatin on REM sleep.