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M₁ Muscarinic Acetylcholine Receptor Agonism Alters Sleep without Affecting Memory Consolidation

¹ Albert-Ludwigs-University Freiburg, Germany, ² University of Pittsburgh School of Medicine, ³ University of California, Irvine

Reprint requests should be sent to Christoph Nissen, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213-2593, or via e-mail: nissenc{at}upmc.edu.

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.