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The Journal of Neuroscience, May 15, 1998, 18(10):3779-3785

Carbachol Stimulates [³⁵S]Guanylyl 5'-(-Thio)-Triphosphate Binding in Rapid Eye Movement Sleep-Related Brainstem Nuclei of Rat

M. Luisa Capece, Helen A. Baghdoyan, and Ralph Lydic

Department of Anesthesia, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033

Carbachol enhances rapid eye movement (REM) sleep when microinjected into the pontine reticular formation of the cat and rat. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic receptors (mAChRs). The present study used in vitro autoradiography of carbachol-stimulated [³⁵S]guanylyl-5'-O-(-thio)-triphosphate ([³⁵S]GTPS) binding to test the hypothesis that carbachol activates mAChRs to induce stimulation of G-proteins in brainstem nuclei contributing to REM sleep generation. The results demonstrate a heterogeneous increase in carbachol-stimulated G-protein activation across rat brainstem. Binding of [³⁵S]GTPS in the presence of carbachol, compared with basal binding, was significantly increased in the laterodorsal tegmental nucleus (75.7%), caudal pontine reticular nucleus (68.9%), oral pontine reticular nucleus (64.5%), pedunculopontine tegmental nucleus (55.7%), and dorsal raphe nucleus (54.0%) but not in the nucleus locus coeruleus. The activation of G-proteins by carbachol was concentration-dependent and antagonized by atropine, demonstrating that G-proteins were activated via mAChR stimulation. The results provide the first direct measures of mAChR-activated G-proteins in brainstem nuclei known to contribute to REM sleep generation.

Key words: autoradiography; dorsal raphe nucleus; G-proteins; laterodorsal tegmental nucleus; locus coeruleus; pedunculopontine tegmental nucleus; pontine reticular formation

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18103779-07$05.00/0

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