Long-term enhancement of REM sleep by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in the pontine reticular formation of the rat

In rats, rapid eye movement (REM) sleep can be elicited by microinjection o f vasoactive intestinal polypeptide (VIP) into the oral pontine reticular n ucleus (PnO). In the present study, we investigated whether this area could also be a REM-promoting target for a peptide closely related to VIP: the p ituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely mov ing chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) indu ced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that c ould be prevented by prior infusion of the antagonist PACAP-(6-27) (3 pmol) into the same site. Moreover, injections of PACAP into the centre of the p osterior PnO resulted in REM sleep enhancement which could last for up to I I consecutive days. Quantitative autoradiography using [I-125]PACAP-27 reve aled the presence in the PnO of specific binding sites with high affinity f or PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very lo w affinity for VIP (IC50 > 1 mu M). These data suggest that PACAP within th e PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC(1) rec eptors which have a much higher affinity for PACAP than for VIP might media te this long-term action of PACAP on REM sleep.