ePoster

Brain-wide effects of cannabinoids, measured by functional ultrasound imaging, show strong correlation with CB1R activation and behavior in awake mice

Samuel Le Meur-Diebolt, Jean-Charles Mariani, Stefan Schulz, Thomas Deffieux, Mickael Tanter, Andrea Kliewer, Zsolt Lenkei
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Samuel Le Meur-Diebolt, Jean-Charles Mariani, Stefan Schulz, Thomas Deffieux, Mickael Tanter, Andrea Kliewer, Zsolt Lenkei

Abstract

The emerging therapeutic and recreational use of cannabinoids calls for a better understanding of their brain effects. Using functional ultrasound (fUS) imaging, we studied the dynamics of the alterations of brain activation and functional connectivity (FC) patterns, measured through the neurovascular coupling, in a 60 minutes period following cannabinoid treatment in awake and behaving C57/BL6J mice. We then correlated these changes with important behavioral and molecular readouts, specifically locomotion, analgesia and CB1 receptor (CB1R) activation, measured by CB1R phosphorylation.Results unveil a robust, dose-dependent and CB1R-specific (i.e. down-regulated by AM251 antagonist pre-treatment) fingerprint of brain activation and FC patterns, both after application of THC, the psychoactive component of marijuana, and CP 55,940, a potent CB1R-agonist, but not after application of CBD. Remarkably, the observed fingerprint reveals significant bilateral dysconnectivity in most cortical and sub-cortical areas. Additionally, significant dysconnectivity is observed between the somatosensory cortex and sub-cortical regions, and between the thalamus and hippocampus. Notably, these alterations correlate well with changes in locomotion and analgesia and with CB1R activation.Our findings show that drug-induced behavioral changes are well correlated with specific brain activation and FC patterns in awake mice. This multimodal imaging approach offers insights into the intricate mechanisms underlying cannabinoid-induced alterations in brain function, enabling future therapeutic avenues targeting the endocannabinoid system.

Unique ID: fens-24/brain-wide-effects-cannabinoids-measured-4f893bb5