Prostaglandin D2 induces sleep when infused into the cerebral ventricle of conscious monkeys.
Hayaishi, O.*, Ueno, R.*, Onoe, H.*, Osama, H.*, Fujita, I.+, Nishino, H.+ and Oomura, Y. +
*Hayaishi Bioinformation Transfer Project, Research Development Corporation
of Japan, Takatsuki 569, Japan.
+National Institute for Physiological Sciences, Okazaki 444, Japan.
In a series of previous experiments from our laboratory, microinjection of prostaglandin (PG) D2, into-the preoptic area of conscious rats and intra-cerebroventricular administration of as little as one fmol/sec of PGD2 to rats were shown to induce physiological sleep. Further, several PG synthetase inhibitors decreased the amount of diurnal sleep of rats indicating that endogeneous PGD2 in brain may regulate daily sleep of rats. In this study, we investigated the effect of PGD2 on daily sleep patterns of monkeys (Macaca mulatta). EEG, EMG and EOG were monitored with monkeys partially restricted on monkey chairs for more than 3 months under the 12:12 hr light dark cycle (07:00-08:00 light on and 19:00-20:00 light off gradually). PGD2 was infused into the lateral ventricle for 6 hrs (11:00-17:00) through the chronically implanted cannula. Control monkeys (artificial CSF was infused) were asleep for 45-60 min/6hr during the experimental session. Intraventricular infusion of PGD2 at 150-2250 pmol/min dose-dependently increased the amount of sleep up to 215.8 min/6hr at 2250 pmol/min PGD2. The sleep caused by PGD2 was physiological i.e. deep slow wave sleep and REM sleep appeared in physiological proportions. The monkey awoke within l hr after the termination of PGD2 infusion. Diarrhea and peripheral vasodilatation were not observed. Further, the nocturnal sleep of the experimental day and daily sleep patterns were not affected by the diurnal infusion of PGD2. These results demonstrate that PGD2 serves as a cerebral sleep regulating substance not only in rodents but also in primates,