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

Cholinergic and PACAPergic systems within the oral pontine reticular nucleu s (PnO) play a critical role in REM sleep generation in rats. In this prese nt work, we have investigated whether REM sleep enhancement induced by carb achol (a cholinergic agonist) or PACAP depends on an interaction between mu scarinic and PACAP receptors. This hypothesis was tested by recording sleep -wake cycles in freely moving rats injected into the PnO with PACAP in comb ination with the muscarinic receptor antagonist atropine, or with carbachol in combination with the PACAP receptor antagonist PACAP6-27. When administ ered alone, PACAP (3 pmol) or carbachol (110 pmol) induced an enhancement o f REM sleep during 8 h (+61%, n = 8; +70%, n = 5), which was totally preven ted by infusion of atropine (290 pmol) for PACAP, or of PACAP6-27 (3 pmol) for carbachol, Quantitative autoradiographic studies indicated that (i) PAC AP (10(-9)-10(-7) M) induced in the PnO an increase (+35%) of the specific binding of the muscarinic antagonist [H-3]quinuclidinyl benzylate, which co uld be completely prevented by PACAP6-27 (IC50 = 8 x 10(-8) FA) and (ii) bo th carbachol and PACAP enhanced [S-35]GTP-gamma -S binding in a concentrati on-dependent manner in the PnO. The maximal increase due to carbachol was s ignificantly higher in the presence (+126%) than in the absence (+102%) of PACAP (0.1 muM). These data showed that interactions between muscarinic and PACAP receptors do exist within the PnO and play a role in the local mecha nisms of REM sleep control in the rat.