Critical Role for M3 Muscarinic Receptors in Paradoxical Sleep Generation in the Cat

In the cat, microdialysis application of 200 μM carbachol to the peri-locus coeruleus a (peri-LCα) of the mediodorsal pontine tegmentum produced a marked (≤5–fold) increase in paradoxical sleep. This effect was blocked by 5–50 μM 4–diphenylacetoxy-N-methylpiperidine methiodide (4–DAMP), an M₁/M₃-selective muscarinic receptor antagonist. In contrast, the effect was not reversed by methoctramine, an M₂-selective antagonist, or pirenzepine, an M₁-selective antagonist, even at concentrations as high as 500 μM. In addition, unilateral application of 5 μM 4–DAMP alone to the peri-LCa induced both a >60% decrease in paradoxical sleep and a state of paradoxical sleep without atonia, whereas 50 μM pirenzepine and 500 μM methoctramine had no effect. Our findings are further evidence for the important role played by the peri-LCα and demonstrate a critical role for M₃ muscarinic cholinergic receptors in the generation of paradoxical sleep.