Rapid Eye Movement (REM) sleep: cholinergic mechanisms

Abstract

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.

The Cholinergic System in Schizophrenia Reconsidered: Anticholinergic Modulation of Sleep and Symptom Profiles

“…We confirmed these findings in another nonoverlapping sample of 20 antipsychotic-naive and 20 drug-free previously medicated schizophrenic patients and 20 healthy controls (Maixner et al 1996). Considering known cholinergic effects on REM latency and other sleep measures Gillin and Sitaram 1984), these data are consistent with the hypothesis of increased cholinergic activity in schizophrenia and its implication in the production of negative symptoms. In related studies (Taylor et al 1991;Maixner et al 1998;Tandon 1997), we observed that polysomnographic measures partially normalized following antipsychotic treatment (with neuroleptics, clozapine, and risperidone).…”

“…Because multiple noncholinergic mechanisms influence both DST response and polysomnographic results, however, these data are suggestive at best and do not lend themselves to any definitive interpretation. In the hope of determining the cholinergic contribution to these abnormalities and providing a more refined index of central cholinergic function than simple baseline parameters, we turned our attention to studying the effects of cholinergic/anticholinergic modulation using polysomnography (Sitaram and Gillin 1980;Gillin and Sitaram 1984).…”

“…Because multiple noncholinergic mechanisms influence both DST response and polysomnographic results, however, these data are suggestive at best and do not lend themselves to any definitive interpretation. In the hope of determining the cholinergic contribution to these abnormalities and providing a more refined index of central cholinergic function than simple baseline parameters, we turned our attention to studying the effects of cholinergic/anticholinergic modulation using polysomnography (Sitaram and Gillin 1980;Gillin and Sitaram 1984).There have been several studies on the effects of cholinergic/anticholinergic challenge on polysomnographic measures in other psychiatric disorders (Berger et al 1989;Poland et al 1997), but this strategy had not been employed in schizophrenia. In an exploratory study (Tandon et al 1991b), we compared the effects of biperiden on sleep measures in 12 schizophrenic patients and 10 normal controls.…”

Melatonin therapy for REM sleep behavior disorder: a critical review of evidence

“…A neurotransmitter mechanism could also play a role in the pathophysiology of RBD as it has been proposed the ratio of cholinergic to aminergic activity facilitates REM sleep,[43] in which acetylcholine has multiple roles. [44] Though report of nightmares and enhanced dreaming with acetylcholinesterase inhibitor poisoning are available,[45] patients with RBD taking acetylcholinesterase inhibitors have been reported to have both lessened response in RBD outcomes [23] as well as improvement. [46] Melatonin inhibits calmodulin which then may modulate skeletal muscle acetylcholine receptors.…”

An 8-week, open-label study to evaluate the effect of sertraline on the polysomnogram of depressive patients with insomnia

“…However, this hypothesis was opposed by some psychiatrists. Gillin administered scopolamine to healthy volunteers for 3 days, and these volunteers developed major sleep disturbances characteristic of depression, including a shortened REM latency, but they did not develop symptoms of depression . Furthermore, in other studies, bupropion and Nefazodone did not suppress REM sleep despite being effective antidepressants.…”