M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.
Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.
Nissen
Christoph
C
Albert-Ludwigs-University Freiburg, Germany. nissenc@upmc.edu
Power
Ann E
AE
Nofzinger
Eric A
EA
Feige
Bernd
B
Voderholzer
Ulrich
U
Kloepfer
Corinna
C
Waldheim
Bernhard
B
Radosa
Marc-Philipp
MP
Berger
Mathias
M
Riemann
Dieter
D
D000328:Adult; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D015999:Multivariate Analysis; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D013388:Succinimides / Q000494:pharmacology*
D018721:Muscarinic Agonists; D013388:Succinimides; C001886:2-ethyl-8-methyl-2,8-diazaspiro(4,5)decane-1,3-dione