L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults
Author(s)
Type
Journal Article
Abstract
INTRODUCTION: Millions of people worldwide take medications such as L-DOPA that increase dopamine to treat Parkinson's disease. Yet, we do not fully understand how L-DOPA affects sleep and memory. Our earlier research in Parkinson's disease revealed that the timing of L-DOPA relative to sleep affects dopamine's impact on long-term memory. Dopamine projections between the midbrain and hippocampus potentially support memory processes during slow wave sleep. In this study, we aimed to test the hypothesis that L-DOPA enhances memory consolidation by modulating NREM sleep. METHODS: We conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65-79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning. RESULTS: The single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1-4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects. DISCUSSION: Our results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slow-wave sleep and long-term memory may have clinical implications. CLINICAL TRIAL REGISTRATION: Eudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064.
Date Issued
2023-04-05
Date Acceptance
2023-03-20
Citation
Frontiers in Behavioral Neuroscience, 2023, 17, pp.1-15
ISSN
1662-5153
Publisher
Frontiers Media S.A.
Start Page
1
End Page
15
Journal / Book Title
Frontiers in Behavioral Neuroscience
Volume
17
Copyright Statement
Copyright © 2023 Isotalus, Carr, Blackman, Averill, Radtke, Selwood, Williams, Ford, McCullagh, McErlane, O’Donnell, Durant, Bartsch, Jones, Muñoz-Neira, Wearn, Grogan and Coulthard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37091594
Subjects
ageing
dopamine
learning
levodopa
memory
NREM
sleep
slow wave sleep
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
1096720
Date Publish Online
2023-04-05