A pharmacological model of paradoxical sleep: The role of cholinergic and monoamine systems

Karczmar, Alexander G.; Longo, Vincenzo; Carolis, A. Scotti de

doi:10.1016/0031-9384(70)90061-2

Cited by 156 publications

(25 citation statements)

References 7 publications

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“…However, it has also been known for a very long time that pharmacological induction of PS, instead of waking, by enhanced ACh also depends on depletion or absence of other neurotransmitters of the arousal systems, such as the monoamines (Karczmar et al, 1970). So, it is likely that induction of PS by cholinergic transmission also depends on the absence of Orx.…”

Section: Regional Distribution Of M2r-and Orx2r-bearing Cells In Relamentioning

confidence: 98%

Muscarinic‐2 and orexin‐2 receptors on GABAergic and other neurons in the rat mesopontine tegmentum and their potential role in sleep–wake state control

Brischoux

Mainville

Jones

2008

J of Comparative Neurology

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Acetylcholine (ACh) plays an important role in the promotion of paradoxical sleep (PS) with muscle atonia through the muscarinic-2 receptor (M2R) in the mesopontine tegmentum. Conversely, orexin (Orx or hypocretin) appears to be critical for the maintenance of waking with muscle tone through the orexin-2 (or hypocretin-B) receptor (Orx2R), which is lacking in dogs having narcolepsy with cataplexy. In dual-immunostained material viewed under fluorescence microscopy, we examined the presence and distribution of M2R or Orx2R labeling on all neuronal nuclei (NeuN)-stained neurons or on glutamic acid decarboxylase (GAD)-stained neurons through the mesopontine tegmentum. Applying stereological analysis, we determined that many neurons bear M2Rs on their membrane ( approximately 6,300), including relatively large, non-GABAergic cells, which predominate (>75%) in the oral and caudal pontine (PnO and PnC) reticular fields, and small, GABAergic cells ( approximately 2,800), which predominate (>80%) in the mesencephalic (Mes) reticular formation. Many neurons bear Orx2Rs on their membrane ( approximately 6,800), including relatively large, non-GABAergic cells, which predominate (>70%) through all reticular fields, and comparatively few GABAergic cells ( approximately 700). In triple-immunostained material viewed by confocal microscopy, many large neurons in PnO and PnC appear to bear both M2Rs and Orx2Rs on their membrane, indicating that ACh and Orx could exert opposing influences of inhibition vs. excitation on putative reticulo-spinal neurons and thus attenuate vs. facilitate activity and muscle tone. A few GABAergic cells bear both receptors and could as PS inhibitor neurons serve under these different influences to control PS effector neurons and accordingly gate PS and muscle atonia appropriately across sleep-wake states.

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Section: Regional Distribution Of M2r-and Orx2r-bearing Cells In Relamentioning

confidence: 98%

Muscarinic‐2 and orexin‐2 receptors on GABAergic and other neurons in the rat mesopontine tegmentum and their potential role in sleep–wake state control

Brischoux

Mainville

Jones

2008

J of Comparative Neurology

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“…Studying the chronic mesencephalic or pontine cat, Jouvet (1962) observed increased duration of REM periods after physostigmine and complete absence of REM sleep after atropine. Likewise, Karczmar et al, (1970) induced REM sleep in the awake cat, rabbit, or rat with physostigmine only if it had been reserpinized or pretreated with the catecholamine synthesis blocker, alpha-methyl-paratyrosine (AMPf). These REM periods were also unusually long, and they could be prevented by pretreatment with atropine.…”

Section: Previous Pharmacological Studies Of Ach and Sleepmentioning

confidence: 99%

Acetylcholine: Possible Involvement in Sleep and Analgesia

Sitaram

Gillin

1979

Brain Acetylcholine and Neuropsychiatric Disease

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“…Domino et al (1968) induced REM-like states in intact cats with physostigmine and arecoline, a muscarinic agonist. Furthermore, on the basis of studies in reserpinized animals, Karczmar et al (1970) found that physostigmine induced REM sleep and proposed that REM sleep is facilitated as the ratio of cholinergic to aminergic activity increases.…”

Section: Administration Of Cholinesterase Inhibitorsmentioning

confidence: 99%

Rapid Eye Movement (REM) sleep: cholinergic mechanisms

Gillin¹,

Sitaram²

1984

Psychol. Med.

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EDITORIALRapid Eye Movement (REM) sleep: cholinergic mechanisms 1 Otto Loewe conceived of the experiment that led to the discovery of Vagusstoff or acetylcholine during a dream. As this review will attempt to show, it is likely that acetylcholine, acting as a neurotransmitter on a muscarinic synapse within the dorsal tegmentum of the pons, triggered the dream that resulted in its own discovery.Evidence for the involvement of acetylcholine with Rapid Eye Movement (REM) sleep comes both from human and animal studies. REM sleep is a complicated state, involving, on the psychological level, dreaming, and, on the physiological, activation of the EEG, bursts of rapid eye movements, atonia of the major antigravity muscles, monophasic waves in the pontine, geniculate and occipital areas (PGO spikes), hippocampal theta waves, variability of autonomic functioning, and increased firing rates of most central neurones (with notable exceptions, to be mentioned later). There is also a circadian propensity to REM sleep in man and many mammals. Acetylcholine may be involved in nearly all aspects of REM sleep. ANIMAL STUDIESSix different types of data from animal studies suggest that acetylcholine plays an important role in REM sleep.

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A pharmacological model of paradoxical sleep: The role of cholinergic and monoamine systems

Cited by 156 publications

References 7 publications

Muscarinic‐2 and orexin‐2 receptors on GABAergic and other neurons in the rat mesopontine tegmentum and their potential role in sleep–wake state control

Muscarinic‐2 and orexin‐2 receptors on GABAergic and other neurons in the rat mesopontine tegmentum and their potential role in sleep–wake state control

Acetylcholine: Possible Involvement in Sleep and Analgesia

Rapid Eye Movement (REM) sleep: cholinergic mechanisms

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