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

Autor: Hanna K. Isotalus, Will J. Carr, Jonathan Blackman, George G. Averill, Oliver Radtke, James Selwood, Rachel Williams, Elizabeth Ford, Liz McCullagh, James McErlane, Cian O’Donnell, Claire Durant, Ullrich Bartsch, Matt W. Jones, Carlos Muñoz-Neira, Alfie R. Wearn, John P. Grogan, Elizabeth J. Coulthard
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Behavioral Neuroscience, Vol 17 (2023)
Druh dokumentu: article
ISSN: 1662-5153
DOI: 10.3389/fnbeh.2023.1096720
Popis: 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.
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