M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation

Preclinical studies have implicated cholinergic neurotransmission, specifically M, muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M-1 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, Pre-sleep 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 M, mAChR activation in healthy humans has no clinically relevant effect oil pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.