Psychedelics, which effects appear to be mediated via seratonin-2A receptors(5-HT2AR), are a promising therapeutic. Recent human studies have shown drastic changes in functional network organization but may be confounded due to Serotonin’s vasoconstriction effects. We aimed to determine if 5-HT2AR agonism (via Lisuride), alone, differentially affect cortical neuronal and hemodynamic activity, functional connectivity (FC), and neurovascular coupling (NVC). Eight Thy1-jRGECO1a mice were imaged for 60-minutes under awake, resting-state conditions using wide-field optical imaging. Lisuride significantly reduced neuronal and hemodynamic bilateral FC and activity in a region- and frequency-band-specific manner. Furthermore, delayed NVC was observed. Results suggest 5-HT2AR agonism alters hemodynamic activity, FC and NVC. Future work will evaluate acute effects of commonly used psychedelics on brain function and differentiate hallucinatory vs non-hallucinatory 5-HT2A receptor activation.
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