Muscarinic and PACAP receptor interactions at pontine level in the rat: significance for REM sleep regulation

• Published in: The European journal of neuroscience 2000-12, Vol.12 (12), p.4496-4504
• Main Authors: Ahnaou, A., Laporte, A. M., Ballet, S., Escourrou, P., Hamon, M., Adrien, J., Bourgin, P.
• Format: Article
• Language: English
• Subjects: Animals; autoradiography; Binding sites; Carbachol - administration & dosage; Carbachol - pharmacology; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; G-proteins; Laboratory animals; Male; Microinjections; muscarinic receptors; Neuropeptides - administration & dosage; Neuropeptides - pharmacology; Neurotransmitter Agents - administration & dosage; Neurotransmitter Agents - pharmacology; PACAP receptors; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Pituitary Adenylate Cyclase-Activating Polypeptide; Polypeptides; Pons - physiology; pontine reticular nucleus; Proteins; Pyramidal Tracts - drug effects; Pyramidal Tracts - physiology; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone - drug effects; Receptors, Pituitary Hormone - physiology; Sleep; Sleep Stages - drug effects; Sleep Stages - physiology; Sleep, REM - drug effects; Sleep, REM - physiology; sleep-wake cycle; Wakefulness - drug effects; Wakefulness - physiology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.0953-816x.2000.01345.x

Cholinergic and PACAPergic systems within the oral pontine reticular nucleus (PnO) play a critical role in REM sleep generation in rats. In this present work, we have investigated whether REM sleep enhancement induced by carbachol (a cholinergic agonist) or PACAP, depends on an interaction between muscarinic and PACAP receptors. This hypothesis was tested by recording sleep–wake cycles in freely moving rats injected into the PnO with PACAP in combination with the muscarinic receptor antagonist atropine, or with carbachol in combination with the PACAP receptor antagonist PACAP6‐27. When administered alone, PACAP (3 pmol) or carbachol (110 pmol) induced an enhancement of REM sleep during 8 h (+61%, n = 8; +70%, n = 5), which was totally prevented by infusion of atropine (290 pmol) for PACAP, or of PACAP6‐27 (3 pmol) for carbachol. Quantitative autoradiographic studies indicated that (i) PACAP (10−9−10−7 m) induced in the PnO an increase (+35%) of the specific binding of the muscarinic antagonist [3H]quinuclidinyl benzylate, which could be completely prevented by PACAP6‐27 (IC50 = 8 × 10−8 m) and (ii) both carbachol and PACAP enhanced [35S]GTP‐γ‐S binding in a concentration‐dependent manner in the PnO. The maximal increase due to carbachol was significantly higher in the presence (+126%) than in the absence (+102%) of PACAP (0.1 µm). These data showed that interactions between muscarinic and PACAP receptors do exist within the PnO and play a role in the local mechanisms of REM sleep control in the rat.