High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin
Molecular Psychiatry – January 17, 2024
Source: OpenAlex
Summary
A compelling Neuroscience finding reveals the hallucinogen Psilocybin acts as an anxiolytic. In larval zebrafish, a model for Psychedelics and Drug Studies, it facilitated exploration and prevented stress responses. This research, crucial for Psychology, shows psilocybin inhibits serotonin neurons in the dorsal raphe nucleus. Understanding this serotonergic neurotransmitter receptor influence on behavior, like insights from Nicotinic Acetylcholine Receptors Study, is vital for drug development to potentially avoid issues like desensitization.
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.