The human brain selectively stores knowledge of the world to optimise future behaviour, automatically rehearsing, contextualising or discarding information to create a robust record of experiences. Storage or forgetting evolves over time, particularly during sleep. We sought to test how dopamine shaped long term memory formation before and during sleep. We administered dopamine (L-DOPA tablet) during learning, re-learning, consolidation or retrieval of word lists in two independent double-blind randomised placebo-controlled cross-over studies of healthy older adults (study 1 n = 35, study 2 n = 32). During consolidation, nocturnal dopamine accelerated forgetting for words presented once, but did not affect words presented twice from forgetting. Overnight dopamine increased total slow wave sleep duration by approximately 11%. The effect of dopamine on memory correlated with increased spindle amplitude, which was maximised near slow oscillation peaks, suggesting dopamine-dependent memory processing modulates spindles dependent on slow-oscillation phase. Pharmaceutical modification of slow wave sleep holds great promise for improving old age – potential benefits could include cognitive enhancement and Alzheimer’s prevention.

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.