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Cholinergic antagonists and REM sleep generation
J Velazquez-Moctezuma1, M Shalauta, J C Gillin
1Department of Psychiatry, San Diego VA Medical Center (V-116A), La Jolla, CA.
Abstract:
In this study we extended our observations on the role of M1 and M2 muscarinic receptors in mediating the cholinergic induction of REM sleep. Cats were chronically implanted with sleep recording electrodes and microinjections of Ringer's or muscarinic antagonists followed by the relatively specific M2 muscarinic agonist, cis-methyl-dioxolane (cisdioxo), were made into the medial pontine reticular formation (mPRF). The microinjection of Ringer's followed by cisdioxo significantly increased REM sleep percentage. Atropine, a mixed muscarinic receptor antagonist, administered before cisdioxo blocked the REM sleep increase while pirenzepine, a selective M1 muscarinic antagonist, did not block the cisdioxo-induced increase in REM sleep. Gallamine, a nicotinic and a putative M2 antagonist, tended to inhibit the cisdioxo-induced increase in REM sleep. These results support the hypothesis that the cholinergic stimulation-induced REM sleep in the medial pontine reticular formation is mediated by a non-M1 muscarinic receptor subtype.
Insights
Cholinergic stimulation of REM sleep in cats is mediated by a non-M1 muscarinic receptor. This study investigated M1 and M2 muscarinic receptors in the brainstem, identifying a specific receptor subtype involved in REM sleep.
Area of Science:
- Neuroscience
- Sleep Research
- Pharmacology
Background:
- Cholinergic pathways in the brainstem are crucial for regulating sleep-wake states.
- Muscarinic receptors, specifically M1 and M2 subtypes, are implicated in mediating cholinergic effects on sleep.
- Previous observations suggested a role for these receptors in the induction of Rapid Eye Movement (REM) sleep.
Purpose of the Study:
- To further investigate the specific roles of M1 and M2 muscarinic receptors in the cholinergic induction of REM sleep.
- To determine the receptor subtype responsible for REM sleep generation in the medial pontine reticular formation (mPRF).
Main Methods:
- Chronic implantation of sleep recording electrodes in cats.
- Microinjections into the medial pontine reticular formation (mPRF) with Ringer's solution or muscarinic antagonists.
- Administration of a specific M2 muscarinic agonist, cis-methyl-dioxolane (cisdioxo), following antagonist or Ringer's solution.
- Assessment of REM sleep percentage changes in response to pharmacological manipulations.
Main Results:
- Microinjection of cisdioxo significantly increased REM sleep percentage.
- Atropine, a mixed muscarinic antagonist, blocked the cisdioxo-induced REM sleep increase.
- Pirenzepine, a selective M1 antagonist, did not block the REM sleep increase.
- Gallamine, a putative M2 antagonist, showed a tendency to inhibit the REM sleep increase.
Conclusions:
- The cholinergic stimulation that induces REM sleep in the mPRF is mediated by a non-M1 muscarinic receptor subtype.
- These findings support the hypothesis that a specific, non-M1 muscarinic receptor is involved in REM sleep generation.
- The results contribute to understanding the neurochemical mechanisms underlying REM sleep regulation.