Pontine nitric oxide modulates acetylcholine release, rapid eye movement sleep generation, and respiratory rate.
Pontine cholinergic neurotransmission is known to play a key role in the regulation of rapid eye movement (REM) sleep and to contribute to state-dependent respiratory depression. Nitric oxide (NO) has been shown to alter the release of acetylcholine (ACh) in a number of brain regions, and previous studies indicate that NO may participate in the modulation of sleep/wake states. The present investigation tested the hypothesis that inhibition of NO synthase (NOS) within the medial pontine reticular formation (mPRF) of the unanesthetized cat would decrease ACh release, inhibit REM sleep, and prevent cholinergically mediated respiratory depression. Local NOS inhibition by microdialysis delivery of N(G)-nitro-L-arginine (NLA) significantly reduced ACh release in the cholinergic cell body region of the pedunculopontine tegmental nucleus and in the cholinoceptive mPRF. A second series of experiments demonstrated that mPRF microinjection of NLA significantly reduced the amount of REM sleep and the REM sleep-like state caused by mPRF injection of the acetylcholinesterase inhibitor neostigmine. Duration but not frequency of REM sleep epochs was significantly decreased by mPRF NLA administration. Injection of NLA into the mPRF before neostigmine injection also blocked the ability of neostigmine to decrease respiratory rate during the REM sleep-like state. Taken together, these findings suggest that mPRF NO contributes to the modulation of ACh release, REM sleep, and breathing.
Leonard
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Department of Anesthesia, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Lydic
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D000109:Acetylcholine / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000187:drug effects; D002415:Cats; D002799:Cholinergic Fibers / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D008959:Models, Neurological; D009388:Neostigmine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D017286:Polysomnography; D011149:Pons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012119:Respiration / Q000187:drug effects / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D010277:Parasympathomimetics; D019335:Nitroarginine; D009569:Nitric Oxide; D009388:Neostigmine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D006221:Halothane