Repeated morphine reorganizes sleep-wake states, cortical and central medial thalamic oscillations, and network synchronization in mice
- 1University of Colorado Anschutz Medical Campus
Abstract
Objectives: Opioids disrupt sleep, but how repeated exposure reorganizes thalamocortical networks is unknown. We asked whether morphine alters sleep architecture, regional oscillations, and phase synchronization, and how exposure history modifies these effects. Methods: From mice, we analyzed cortical electroencephalogram (EEG), central medial thalamic (CMT) local field potentials (LFP), and electromyography (EMG) for 24h after the first and fourth injections of morphine and in abstinence, and quantified vigilance-state occupancy, spectral power, state-power correlations, and the weighted phase-lag index (wPLI), which minimizes volume conduction. Results: Morphine produced hyperlocomotion, wake promotion persisting with repeated exposure, non-rapid eye movement (NREM) sleep suppression, complete rapid eye movement (REM) sleep loss, and rebound sleep. Cortex and thalamus dissociated: in NREM sleep after the first injection, cortical delta and low-gamma power increased, while CMT delta, theta, alpha, and beta power decreased. NREM occupancy coupled more strongly to CMT delta and theta power after both injections, whereas cortical wake correlations in theta, alpha, and beta fell and reversed during abstinence. Overall synchronization was altered only in theta and alpha: corticocortical alpha synchronization decreased acutely, and repeated exposure reduced thalamocortical theta synchronization in wake and NREM sleep. During abstinence, sleep architecture and synchronization largely normalized while spectral and state-power abnormalities persisted alongside mechanical hypersensitivity. Conclusions: We found that morphine does not merely reduce sleep; it reorganizes it: cortex and CMT move in opposite directions, thalamocortical phase synchronization is redistributed, and the resulting spectral and state-power abnormalities outlast the recovery of sleep architecture itself rather than producing tolerance.
Related
- Repeated cocaine reorganizes striatal ensembles along the ventral-dorsal axis
- Parvalbumin interneuron maturation reorganizes cortical population activity structure during development
- Awake sharp-wave ripples coincide with rhythmic cortical synchronization
- Resting Cortical Alpha and Beta Oscillations are Continuous Across Space and Frequency
- Cortical high frequency oscillations reflect encoding and retrieval of specific word concepts
BibTeX
@misc{tadic2026repeated,
title = {{Repeated morphine reorganizes sleep-wake states, cortical and central medial thalamic oscillations, and network synchronization in mice}},
author = {V. Tadic and M. Walz and S. Todorovic and T. Timic Stamenic},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.752991},
url = {https://www.biorxiv.org/content/10.64898/2026.09.20.752991v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Repeated morphine reorganizes sleep-wake states, cortical and central medial thalamic oscillations, and network synchronization in mice
AU - V. Tadic
AU - M. Walz
AU - S. Todorovic
AU - T. Timic Stamenic
PY - 2026
DA - 2026/09/20
PB - bioRxiv
DO - 10.64898/2026.09.20.752991
UR - https://www.biorxiv.org/content/10.64898/2026.09.20.752991v1
AB - Objectives: Opioids disrupt sleep, but how repeated exposure reorganizes thalamocortical networks is unknown. We asked whether morphine alters sleep architecture, regional oscillations, and phase synchronization, and how exposure history modifies these effects. Methods: From mice, we analyzed cortical electroencephalogram (EEG), central medial thalamic (CMT) local field potentials (LFP), and electromyography (EMG) for 24h after the first and fourth injections of morphine and in abstinence, and quantified vigilance-state occupancy, spectral power, state-power correlations, and the weighted phase-lag index (wPLI), which minimizes volume conduction. Results: Morphine produced hyperlocomotion, wake promotion persisting with repeated exposure, non-rapid eye movement (NREM) sleep suppression, complete rapid eye movement (REM) sleep loss, and rebound sleep. Cortex and thalamus dissociated: in NREM sleep after the first injection, cortical delta and low-gamma power increased, while CMT delta, theta, alpha, and beta power decreased. NREM occupancy coupled more strongly to CMT delta and theta power after both injections, whereas cortical wake correlations in theta, alpha, and beta fell and reversed during abstinence. Overall synchronization was altered only in theta and alpha: corticocortical alpha synchronization decreased acutely, and repeated exposure reduced thalamocortical theta synchronization in wake and NREM sleep. During abstinence, sleep architecture and synchronization largely normalized while spectral and state-power abnormalities persisted alongside mechanical hypersensitivity. Conclusions: We found that morphine does not merely reduce sleep; it reorganizes it: cortex and CMT move in opposite directions, thalamocortical phase synchronization is redistributed, and the resulting spectral and state-power abnormalities outlast the recovery of sleep architecture itself rather than producing tolerance.
ER -