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

Abstract

Serotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. 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 found that acute psilocybin treatment has two behavioral effects: [i] facilitation of spontaneous exploration (“stimulatory”) and [ii] prevention of irregular swim patterns following stress exposure (“anxiolytic”). These effects differed from the effect of acute SSRI treatment and were rather similar to the effect of ketamine treatment. Neural activity imaging in the dorsal raphe nucleus suggested that psilocybin inhibits serotonergic neurons by activating local GABAergic neurons, consistent with psychedelic-induced suppression of serotonergic neurons in mammals. These findings pave the way for using larval zebrafish to elucidate neural mechanisms underlying the behavioral effects of serotonergic psychedelics.

Behavioral Studies of Zebrafish Reveal a New Perspective on the Reproductive Toxicity of Micro- and Nanoplastics

“…Technological advancements in video recording and analysis have enhanced behavioral assessments [ 158 ]. Three-dimensional behavior analysis is capable of analyzing more complex behavior characteristics and is also capable of finding the unique behavior characteristics of zebrafish and evaluating them [ 159 ].…”

“…Open access. ( e ) High-resolution and high-speed tracking of zebrafish behavior in large environment [ 158 ]. Open access.…”

A scoping review of the effects of mushroom and fungus extracts in rodent models of depression and tests of antidepressant activity

“…Searches were also conducted using specific behavioural models/tests or mushroom species as keywords. Studies were limited to those using rodent species as those reflect the expertise of the authors ( Lu et al, 2005 ; Barr et al, 2006 ; Hill et al, 2007 ; Boyda et al, 2014 ); however, it is important to note that other species, such as zebrafish, represent additional valid animal models of antidepressant efficacy ( Braun et al, 2024 ).…”

“…The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar. 2024…”