Critical role for M3 muscarinic receptors in paradoxical sleep generation in the cat.

In the cat, microdialysis application of 200 microM carbachol to the peri-locus coeruleus alpha (peri-LC alpha) of the mediodorsal pontine tegmentum produced a marked (< or = 5-fold) increase in paradoxical sleep. This effect was blocked by 5-50 microM 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 microM. In addition, unilateral application of 5 microM 4-DAMP alone to the peri-LC alpha induced both a > 60% decrease in paradoxical sleep and a state of paradoxical sleep without atonia, whereas 50 microM pirenzepine and 500 microM methoctramine had no effect. Our findings are further evidence for the important role played by the peri-LC alpha and demonstrate a critical role for M3 muscarinic cholinergic receptors in the generation of paradoxical sleep.