ArticleThe Journal of pharmacology and experimental therapeutics2025
Spontaneous daily sleep disruptions associated with morphine dependence and withdrawal in rats.
Article in The Journal of pharmacology and experimental therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Repeated morphine reorganizes sleep-wake states, cortical and central medial thalamic oscillations, and network synchronization in mice.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
Sleep disturbances are prominent symptoms of opioid withdrawal that contribute to relapse in individuals with opioid use disorder (OUD). Although preclinical studies often examine protracted withdrawal after sustained abstinence, few address the repeated, spontaneous withdrawal cycles that model human patterns of use. Moreover, targeting sleep disruptions provides a novel strategy to reduce relapse risk. The present studies characterized the effects of repeated spontaneous daily withdrawal on sleep and quantitative electroencephalography (qEEG) after once-daily morphine administration in male Sprague-Dawley rats. Daily withdrawal produced persistent sleep disruptions, including reduced rapid eye movement (REM) and non-REM sleep, increased time awake, and sleep fragmentation. Notably, tolerance did not develop to the acute pharmacological effects of morphine or spontaneous daily withdrawal effects on sleep across the 30-day study. Relative spectral analysis (qEEG) revealed progressive shifts from low (δ) to high (γ) frequency power across withdrawal phases, with significant and persistent increases in wake and non-REM relative γ band power during later stages of daily and protracted withdrawal. There were few correlations between somatic behavioral signs and sleep or qEEG supporting our hypothesis that sleep, and brain activity disturbances represent distinct withdrawal phenotypes that should be studied and treated separately from somatic withdrawal behaviors. Together, these findings highlight the chronic and multifaceted nature of opioid withdrawal, particularly its effect on disrupted sleep and brain activity. Collectively, these studies characterized a translationally relevant preclinical model incorporating both sleep and qEEG as potential behavioral and physiological biomarkers for evaluating putative pharmacotherapies for withdrawal-related sleep dysfunction in OUD. SIGNIFICANCE STATEMENT: Sleep disruptions associated with withdrawal in opioid use disorder represent a contributing factor for relapse yet lack targeted treatments. This study reports consistent, spontaneous daily sleep disruptions in rats after once-daily morphine administration, providing a model that can be used for treatment development.
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