Strong rebound of wakefulness follows prostaglandin D₂‐ or adenosine A_2a receptor agonist‐induced sleep

Abstract

SUMMARYWe studied the effect of sleep excess on the sleep-wakefulness pattern of rats.Subarachnoid infusion of prostaglandin D 2 or the adenosine A 2a receptor agonist CGS21680 effectively induced slow wave sleep (SWS) for the first 12 h of the nighttime period, whereas they did not induce sleep during the following 24 h of infusion. An increase in the amount of wakefulness was seen during the last 12 h of prostaglandin D 2 infusion. The amounts of wakefulness strongly increased during the following 36-h recovery period. Rebound wakefulness was extraordinarily strong after the cessation of CGS21680 infusion, reaching almost complete insomnia during the night-time. Treatment of animals with prostaglandin D 2 overnight, following by treatment with CGS21680 on the next night, resulted in the strongest induction of wakefulness rebound. During the rebound period, the amount of wakefulness reached up to 50 min per hour in the daytime. Rebound of wakefulness depended on the amounts of preceding SWS induced by infusion of prostaglandin D 2 for 6 or 12 h and of CGS21680 for 12 h. The larger the amount of SWS, the larger the amount of the following rebound of wakefulness. Rebounds of wakefulness occurred as a result of decrease in SWS amounts, whereas paradoxical sleep amounts did not change. Desensitization of adenosine A 2a receptors and accumulation of prostaglandin E 2 may be involved in the production of strong wakefulness rebound following relatively long treatments (more than 12 h) with prostaglandin D 2 or CGS21680.

Dominant localization of prostaglandin D receptors on arachnoid trabecular cells in mouse basal forebrain and their involvement in the regulation of non-rapid eye movement sleep

“…The PGD 2 infusion at a higher dose (50 pmol͞min) increased NREM sleep of WT mice to the maximum sleep level during the day time (Ϸ60 min͞2 h) but did not induce rebound wakefulness observed after the cessation of the infusion. These results are in good agreement with our previous findings that NREM sleep was selectively induced by PGD 2 infusion into the subarachnoid space of the rat basal forebrain (2) and that the rebound wakefulness was not observed after induction of an excess NREM sleep by PGD 2 infusion for 36 h (30). Therefore, we consider PGD 2 is potentially useful for the development of a somnogenic drug without side effects such as weak rebound of wakefulness.…”

Arousal effect of orexin A depends on activation of the histaminergic system

“…The probe was continuously perfused with artificial cerebrospinal fluid (140 mM NaCl͞3 mM KCl͞1.0 mM MgCl 2 ͞1.3 mM CaCl 2 ͞2 mM Na 2 HPO 4 ͞2 mM NaH 2 PO 4 , pH 7.4) at a flow rate of 2 l/min. The EEG͞EMG signals were amplified and filtered (EEG, 0.5-30 Hz; EMG, 16-128 Hz), then digitized at a sampling rate of 128 Hz and recorded by using a data acquisition program SLEEPSIGN (Kissei Comtec, Nagano, Japan) as de- scribed (38). Baseline and experimental recordings were taken in each rat for 2 consecutive 24-hr periods, starting at 8 a.m. On the experimental day, orexin A, at a dose of 1, 5, or 25 pmol/2 l per min, was perfused from 9 to 10 a.m. in the experimental group.…”

“…The vigilance states were automatically classified off-line by 4-s epochs for mice and 10-s epochs for rats, into three stages of wake, NREM, and REM sleep by SLEEPSIGN, according to the standard criteria (38,40,41). As a final step, defined sleep-wake stages were examined visually, and corrected, if necessary.…”

Mastocytosis: Mediator-Related Signs and Symptoms

“…The frequency and morphology of mast cells in the brain in SM patients have not been studied and measurements of mediators in the brain are lacking. PGD 2 has been implicated in sleep/awake patterns based on the findings in transgenic mice and rats [32, 33]. …”