REM Sleep Induction by Physostigmine Infusion During Sleep

Abstract

Physostigmine (an anticholinesterase agent that increases acetylcholine at the synapse), in a dose of 0.5 milligram, was given intravenously to seven normal human volunteers. When injected during rapid eye movement (REM) sleep, physostigmine woke the subjects, and when injected during non-REM sleep, it induced REM sleep. This result suggests that cholinergic mechanisms play a role in the induction of REM sleep and in modulating cortical arousal mechanisms.

Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

“…These findings are consistent with those from previous clinical (Sitaram et al, 1976;Riemann et al, 1994;Schredl et al, 2001;Kanbayashi et al, 2002) and preclinical studies (eg Calvo et al, 1992). They showed an increase of the number of REMs and REM sleep maintenance after the administration of numerous ACh-esterase inhibitors.…”

“…This finding is consistent with those of previous studies investigating the effects of RS-86 on REM latency in healthy subjects (Riemann et al, 1988;Lauer et al, 2004). The finding that numerous ACh-esterase inhibitors shorten REM latency (eg physostigmine; Sitaram et al, 1976) is consistent but does not further contribute to the discussion of the involvement of AChR subtypes. As in previous studies in younger healthy subjects (Kanbayashi et al, 2002;Perlis et al, 2002), donepezil did not significantly alter REM sleep latency in comparison to placebo.…”

“…Consistently, LDT/PPT neurons demonstrate higher discharge rates during REM sleep (el Mansari et al, 1989). In humans, REM sleep is enhanced after administration of ACh-esterase inhibitors (Sitaram et al, 1976;Riemann et al, 1994) or cholinergic agonists (Spiegel, 1984;Riemann et al, 1988) and inhibited by anticholinergics (Sagales et al, 1969).…”

“…In humans, numerous ACh-esterase inhibitors (eg physostigmine: Sitaram et al, 1976;galanthamine: Riemann et al, 1994) and selective M 1 mAChR agonists, like pilocarpine (Berkowitz et al, 1990) or RS-86 (Riemann et al, 1988), shorten REM latency. Gillin et al (1991) demonstrated that low doses of the M 1 antagonist biperiden selectively enhanced REM latency without affecting REM duration.…”

Contribution of Sleep Physiology to Depressive Pathophysiology

“…The basic mechanisms unraveled in animals are at least partially paralleled in human studies combining EEG sleep with pharmacological probes. For instance, REM sleep is suppressed following systemic 5-HT 1A agonists (Gillin et al 1994;Seifritz et al 1996) and promoted following cholinergic agonists (Sitaram et al 1976;Berger et al 1985;Gillin et al 1991b;. Muscarinic receptor antagonists, on the other hand, partially suppress REM sleep (Gillin et al 1991a), and the depletion of central serotonin enhances REM sleep Moore et al 1998Moore et al , 2001Voderholzer et al 1998).…”