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

Eur J Neurosci. 1999 Nov;11(11):4051-8. doi: 10.1046/j.1460-9568.1999.00811.x.


In rats, rapid eye movement (REM) sleep can be elicited by microinjection of vasoactive intestinal polypeptide (VIP) into the oral pontine reticular nucleus (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 pituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely moving chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) induced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that could 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 posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days. Quantitative autoradiography using [125I]PACAP-27 revealed the presence in the PnO of specific binding sites with high affinity for PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very low affinity for VIP (IC50 > 1 microM). These data suggest that PACAP within the PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC1 receptors which have a much higher affinity for PACAP than for VIP might mediate this long-term action of PACAP on REM sleep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Mapping
  • Brain Stem / drug effects
  • Brain Stem / physiology*
  • Male
  • Microinjections
  • Neuropeptides / administration & dosage
  • Neuropeptides / pharmacology*
  • Neurotransmitter Agents / administration & dosage
  • Neurotransmitter Agents / pharmacology*
  • Peptide Fragments / pharmacology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pons / drug effects
  • Pons / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reticular Formation / drug effects
  • Reticular Formation / physiology*
  • Sleep, REM / drug effects*
  • Sleep, REM / physiology
  • Time Factors
  • Vasoactive Intestinal Peptide / administration & dosage
  • Vasoactive Intestinal Peptide / pharmacology
  • Wakefulness / drug effects


  • Adcyap1 protein, rat
  • Neuropeptides
  • Neurotransmitter Agents
  • Peptide Fragments
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • pituitary adenylate-cyclase-activating peptide (6-27)
  • Vasoactive Intestinal Peptide