L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults

Frontiers in Behavioral Neuroscience

Neuroscience

Carlos Muñoz-Neira¹  James McErlane¹  Rachel Williams¹  George G. Averill¹  Will J. Carr¹  Alfie R. Wearn¹  Elizabeth Ford¹  Hanna K. Isotalus²  John P. Grogan³  James Selwood⁴  Jonathan Blackman⁴  Elizabeth J. Coulthard⁴  Oliver Radtke⁵  Claire Durant⁶  Liz McCullagh⁷  Cian O’Donnell⁸  Matt W. Jones⁹  Ullrich Bartsch⁹ 

[1] Clinical Neurosciences, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom;Clinical Neurosciences, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom;Digital Health, Faculty of Engineering, University of Bristol, Bristol, United Kingdom;Clinical Neurosciences, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom;Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom;School of Psychology, Trinity College Dublin, Dublin, Ireland;Clinical Neurosciences, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom;Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom;Department of Neurosurgery, Heinrich-Heine-University Clinic, Düsseldorf, Germany;Experimental Psychology, University of Bristol, Bristol, United Kingdom;Production Pharmacy, Bristol Royal Infirmary, University Hospitals Bristol and Weston NHS Trust, Bristol, United Kingdom;School of Computer Science, Electrical and Electronic Engineering, and Engineering Mathematics, University of Bristol, Bristol, United Kingdom;School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom;

关键词: sleep;    memory;    dopamine;    ageing;    slow wave sleep;    NREM;    levodopa;    learning;   

DOI  :  10.3389/fnbeh.2023.1096720

 received in 2022-11-12, accepted in 2023-03-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionMillions 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.MethodsWe 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.ResultsThe 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.DiscussionOur 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 registrationEudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064.

【 授权许可】

Unknown   
Copyright © 2023 Isotalus, Carr, Blackman, Averill, Radtke, Selwood, Williams, Ford, McCullagh, McErlane, O’Donnell, Durant, Bartsch, Jones, Muñoz-Neira, Wearn, Grogan and Coulthard.