S01-201 - COMP360 psilocybin increases high gamma and decreases low theta and delta power and coherence within and between prefrontal cortex and dorsal hippocampus of urethane-anaesthetised rats

Session Name
1510 - Poster Session 01 - Section: Emergent Dynamics in Neural Networks (ID 501)
Date
10.07.2022
Session Time
09:30 AM - 01:00 PM

Abstract

Abstract Body

Background and Aims

Psilocybin is a serotonergic psychedelic compound with great psychotherapeutic potential, however, its neural effects are not well understood. Psilocybin’s profound cognition-, perception- and emotion-altering effects are associated with fMRI signal changes in human prefrontal cortex (PFC) and hippocampus, key structures in self-referential information processing. As these regions’ functions rely on their orchestrated electrical oscillatory activity, our study aimed to evaluate psilocybin’s effect on neural oscillations within and between these regions.

Methods

Multi-electrode arrays were inserted into the PFC (prelimbic cortex: PrL) and dorsal hippocampus (CA1) of urethane-anaesthetised adult male Lister Hooded rats. Local field potentials were recorded continuously during 20 min baseline, 60 min post-saline and 90 min post-dose with COMP360 (COMPASS Pathways’ proprietary formulation of psilocybin; 3mg/kg i.p.) to evaluate power spectral and coherence changes.

Results

COMP360 induced a 10- and 32-fold increase in high frequency gamma (51-75 Hz) power in the PrL and CA1, respectively, and a 28-fold increase in PrL–CA1 high gamma coherence. These changes co-occurred with a decrease in low theta (3-5 Hz) and delta (0.5-3 Hz) power within each region.

Conclusion

COMP360 alters the activity within, and communication between, prelimbic cortex and hippocampal area CA1 in the rat, two brain regions whose functional equivalents in humans are strongly implicated in the pathophysiology of psychiatric disease. It remains to be seen to what extent these drug-induced changes in an anaesthetised rodent model can be related to COMP360’s therapeutic mechanism of action in humans.

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