Awaking effect of prostaglandin E 2 in freely moving rats

Abstract

The awaking effect of prostaglandin (PG) E 2 was further examined in a long-term bioassay system. PGE 2 in saline solution was infused between 11.00 and 17.00 h at 0.1, 1, 10, and 100 pmol/min (infusion volume 10 μl/h) into the third cerebral ventricle of freely moving rats. These rats were otherwise infused with saline continuously and exhibited a circadian cycle, spending 70% of the daytime and 37% of the night in sleep. In the rats that received PGE 2 infusion at 1, 10 and 100 pmol/min, slow wave sleep (SWS) decreased to 84%, 69% and 71% and paradoxical sleep (PS) to 85%, 37% and 40% of the paired controls. Thus, the effect of PGE 2 was not specific to either SWS or PS. No effects were observed in the rats that received PGE 2 at 0.1 pmol/min. After PGE 2 infusion at 10 and 100 pmol/min, marked rebounds of both SWS and PS occurred during the night. SWS reduction by PGE 2 was due to the shortened duration of SWS episodes, while SWS increase in the rebound phase was due to the increased number of episodes. PS reduction was due to both the shortened duration and decreased number of PS episodes and PS rebound was due to both the prolonged duration and increased number of episodes. The circadian sleep-wake cycle returned to the baseline on the first or second recovery day after PGE 2 infusion. Sleep reduction by PGE 2 was accompanied by elevation of the brain temperature and rebound increase of sleep occurred with the fall of the brain temperature. On the basis of these findings, we conclude that PGE 2 has a central awaking effect without irreversible damage to the sleep-wake regulating mechanism and that the magnitude of the effect depends on the amount of PGE 2 at the site of action in the brain.