P.0298 Evaluation of the acute mechanism of action of psilocybin in mice

Erkizia-Santamaría, I.; Alles-Pascual, R.; Horrillo, I.; Meana, J.J.; Ortega, Jorge E.

doi:10.1016/j.euroneuro.2021.10.282

Cited by 1 publication

(2 citation statements)

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“…Our observations open up new opportunities for further investigations into subcortical neural mechanisms by which psilocybin affects behaviors. While psilocybin is known primarily as an agonist for type 2 serotonin receptors, it also activates HTR1 receptors to exert its behavioral effects 57,58 . Type 1 receptors are densely expressed in the brainstem areas of mammals 84,85 and zebrafish 86 , whereas type 2 receptors densely express in cerebellar areas of mammals [87][88][89] and zebrafish 90 .…”

Section: Discussionmentioning

confidence: 99%

“…Psilocin crosses the blood-brain barrier 55 and has stronger affinities to serotonin receptors (Figure 3A). Psilocin has affinities to multiple types of serotonin receptors, including inhibitory HTR1 receptors and excitatory HTR2 receptors [56][57][58] . Serotonin receptors in zebrafish are highly similar to those in humans and include major types from HTR1 to HTR7 and their subtypes.…”

Section: Psilocybin Has Stimulatory Effects On Spontaneous Explorationmentioning

confidence: 99%

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High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin

Braun

Rosenberg

Haruvi

et al. 2023

Preprint

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Serotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. Zebrafish have evolutionarily conserved serotonergic circuits and subcortical targets such as the brainstem regions and the cerebellum, providing a promising model for studying the subcortical effects of serotonergic drugs. Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist. Machine learning analyses of precise body kinematics identified latent behavioral states reflecting spontaneous exploration, visually-driven rapid swimming, and irregular swim patterns following stress exposure. Using this method, we identified two main behavioral effects of acute psilocybin treatment: [i] increased rapid swimming in the absence of visual stimuli and [ii] prevention of irregular swim patterns following stress exposure. Together, these effects indicate that psilocybin induces a brain state that is both stimulatory and anxiolytic. These findings pave the way for using larval zebrafish to elucidate subcortical mechanisms underlying the behavioral effects of serotonergic psychedelics.

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