High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin
Dotan Braun, Ayelet M Rosenberg, Elad Rabaniam, Ravid Haruvi, Dorel Malamud, Rani Barbara, Tomer Aiznkot, Berta Levavi‐sivan, Takashi Kawashima
Molecular Psychiatry January 17, 2024 DOI: 10.1038/s41380-023-02391-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Larval zebrafish |
| Interventions | Psilocybin SSRI Ketamine |
| Topics | Psilocybin Serotonin |
| Keywords | Anxiolytic Dorsal raphe nucleus Hallucinogen Desensitization medicine Zebrafish |
| Citations | 32 |
| Key findings | Psilocybin facilitates spontaneous exploration and prevents stress-induced irregular swim patterns in larval zebrafish, likely by inhibiting serotonergic neurons via activation of local GABAergic neurons in the dorsal raphe nucleus. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 12
- Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance. Neuron February 5, 2025
- Neurobiology of psilocybin: a comprehensive overview and comparative analysis of experimental models Frontiers in Systems Neuroscience August 5, 2025
- The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field Neuroscience & Biobehavioral Reviews May 9, 2025
- A scoping review of the effects of mushroom and fungus extracts in rodent models of depression and tests of antidepressant activity Frontiers in Pharmacology June 3, 2024
- Hormonal Influences on Psilocybin Responsivity Across the Female Lifespan: Toward Personalized Psychedelic-Assisted Therapy Psychoactives November 2, 2025
and 7 more in the library
Cites 26
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
and 21 more in the library