Prostaglandin E (EP) receptor subtypes and sleep: promotion by EP4 and inhibition by EP1/EP2.

Prostaglandin (PG) E2 reportedly augmented wakefulness when continuously infused into the third ventricle of the rat brain, whereas it promoted sleep when continuously infused into the subarachnoid space of the ventral surface zone of the rostral basal forebrain, which was designated previously as a PGD2-sensitive sleep-promoting zone (PGD2-SZ). In the present study, we investigated the effects of PGE (EP)-receptor agonists on sleep-wakefulness activities by infusing agonists into the third ventricle or into the subarachnoid space of the PGD2-SZ. Our results indicated that the waking effect is mediated by EP1 and EP2 receptors situating around the third ventricle, whereas the sleep-promoting effect is brought about mainly through activation of EP4 receptors located at or near the subarachnoid space of the PGD2-SZ.