CSF LEVELS OF PROSTAGLANDINS, ESPECIALLY THE LEVEL OF PROSTAGLANDIN D-2, ARE CORRELATED WITH INCREASING PROPENSITY TOWARDS SLEEP IN RATS

The concentration of PGD(2), PGE(2) and of PGF(2 alpha) was measured i n the cerebrospinal fluid (CSF) collected from the cistema magna of co nscious rats (n = 29), which, chronically implanted with a catheter fo r the CSF sampling, underwent deprivation of daytime sleep. Significan t elevation of the CSF level of PGD(2) was observed following 2.5-h sl eep deprivation (SD), and the elevation became more marked following 5 - and 10-h SD, apparently reaching the maximum at 5-h SD (703 +/- 140 pg/ml (mean +/- S.E.M.) for baseline vs. 1734 +/- 363 pg/ml for SD, n = 10). The levels of PGE(2) and PGF(2 alpha) also significantly increa sed following 5- and 10-h SD, but not following 2.5-h SD. It is unlike ly that these changes were simply caused by some responses of the anim als to stress stimuli, because stress stimuli derived from restraint o f the animal at the supine position to a board for 1 h did not produce any acute responses in the CSF levels of prostaglandins (n = 13). In a different group of animals (n = 11) implanted with electrodes for re cording electroencephalogram (EEG) and electromyogram (EMG) in additio n to the catheter, the levels of the prostaglandins in CSF were determ ined for slow-wave sleep (SWS) and wakefulness in the day and for SWS and wakefulness in the night. The highest PGD(2) value was obtained at daytime SWS, whereas the lowest was at night wakefulness; furthermore , a significant difference was observed between SWS and wakefulness ra ther than between day and night. The CSF level of PGE(2) also showed a similar tendency. In an additional group of animals (n = 6), not only PGD(2) but also PGE(2) and PGF(2 alpha) significantly increased the s leeping time of the animal when applied into the subarachnoid space un derlying the ventral surface area of the rostral basal forebrain, the previously defined site of action for the sleep-promoting effect of PG D(2). The promotion of sleep by PGE(2) applied to the subarachnoid spa ce was an effect completely opposite to the well-established awaking e ffect of the same prostaglandin demonstrated in the hypothalamic regio n in a series of previous studies. Based on these results, we conclude that increases in CSF levels of prostaglandins, especially that of PG D(2), are correlated in rats with heightened propensity towards sleep and further with the depth of sleep under normal as well as SD conditi ons. (C) 1997 Elsevier Science B.V.