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bioRxiv · 10.1101/2024.07.30.604249

Opioid-Induced Inter-regional Dysconnectivity Correlates with Analgesia in Awake Mouse Brains

Mariani, J.-C.·Diebolt, S.·Beynac, L.·Santos, R.·Schulz, S.·Deffieux, T.·Tanter, M.·LENKEI, Z.·Kliewer, A.
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Abstract

The {micro}-opioid receptor (MOP) is crucial for both the therapeutic and addictive effects of opioids. Using a multimodal experimental approach, here we combined awake functional ultrasound (fUS) imaging with behavioral and molecular assessments, to examine opioid-induced changes in brain activation and functional connectivity (FC). Morphine, fentanyl, and methadone induce significant dose- and time-dependent reorganization of brain perfusion, oscillations and FC in awake mice. Notably, opioids induce a transient, region-specific hyperperfusion, followed by a consistent MOP-specific dysconnectivity marked by decreased FC of the somatosensory cortex to hippocampal and thalamic regions, alongside increased subcortical and intra-cortical FC. These FC changes temporally correlate with generalized brain MOP activation and analgesia, but not with hypermobility and respiratory depression, suggesting a reorganization of inter-regional FC as a key opioid effect.

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Mariani, J.-C., Diebolt, S., Beynac, L., Santos, R., Schulz, S., Deffieux, T., Tanter, M., LENKEI, Z., Kliewer, A.. 2024-07-31. Opioid-Induced Inter-regional Dysconnectivity Correlates with Analgesia in Awake Mouse Brains. https://doi.org/10.1101/2024.07.30.604249

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