Developmental Neurotoxicity Screen of Psychedelics and Other Drugs of Abuse in Larval Zebrafish (<i>Danio rerio</i>)

Tombari, Robert J.; Mundy, Paige C.; Morales, Kelly M; Dunlap, Lee E.; Olson, David E.; Lein, Pamela J.

doi:10.1021/acschemneuro.2c00642

Cited by 7 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The potential developmental neurotoxicity of LSD, psilocybin, and DMT was evaluated in the larval zebrafish ( Danio rerio ) model (Tombari et al, 2023). None of the compounds caused statistically significant teratological effects or changes in photomotor behavior; however, LSD was shown to increase anxiety‐like behavior in zebrafish embryos, typically observed as erratic movements, after acute and chronic exposure (Tombari et al, 2023).…”

Section: Resultsmentioning

confidence: 99%

The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits

Videira,

Nair,

Paquet

et al. 2023

J of Applied Toxicology

View full text Add to dashboard Cite

Serotonergic psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), and 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT), are currently being investigated for the treatment of psychiatric disorders such as depression and anxiety. Clinical trials with psilocybin and LSD have shown improvement in emotional and psychological scores. Although these drugs are reported to be safe in a controlled environment (such as clinical trials), exposure to low doses of these drugs can result in psychedelic effects, and therefore, occupational safety is an important consideration to prevent adverse effects in the workplace from low daily exposure. This article will discuss the factors involved in the derivation of occupational exposure limits (OELs) and risk assessment of these psychedelic drugs. To support the OEL derivations of psychedelic drugs, information regarding their mechanism of action, adverse effect profiles, pharmacokinetics, clinical effects, and nonclinical toxicity were considered. Additionally, psilocybin and LSD, which are the most extensively researched psychedelic substances, are employed as illustrative examples in case studies. The OELs derived for psilocybin and for LSD are 0.05 and 0.002 μg/m3, respectively, which indicates that these are highly hazardous compounds, and it is important to take into account suitable safety measures and risk‐management strategies in order to minimize workplace exposure.

show abstract

Section: Resultsmentioning

confidence: 99%

The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits

Videira,

Nair,

Paquet

et al. 2023

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…Commonly analysed parameters in larval behavioural tests include total time of motion, distance travelled, speed, acceleration, freezing in light or dark conditions. Many neurotoxic substances, including acrylamide ( Park et al, 2021 ), 6-hydroxydopamine ( Zhang et al, 2017 ), 3,4-methylenedioxyamphetamine ( Tombari et al, 2023 ), fenpropathrin ( Yu et al, 2022 ) have been shown to reduce larval motor activity.…”

Section: Behaviourmentioning

confidence: 99%

Temperature- and chemical-induced neurotoxicity in zebrafish

Toni,

Arena,

Cioni

et al. 2023

Front. Physiol.

View full text Add to dashboard Cite

Throughout their lives, humans encounter a plethora of substances capable of inducing neurotoxic effects, including drugs, heavy metals and pesticides. Neurotoxicity manifests when exposure to these chemicals disrupts the normal functioning of the nervous system, and some neurotoxic agents have been linked to neurodegenerative pathologies such as Parkinson’s and Alzheimer’s disease. The growing concern surrounding the neurotoxic impacts of both naturally occurring and man-made toxic substances necessitates the identification of animal models for rapid testing across a wide spectrum of substances and concentrations, and the utilization of tools capable of detecting nervous system alterations spanning from the molecular level up to the behavioural one. Zebrafish (Danio rerio) is gaining prominence in the field of neuroscience due to its versatility. The possibility of analysing all developmental stages (embryo, larva and adult), applying the most common “omics” approaches (transcriptomics, proteomics, lipidomics, etc.) and conducting a wide range of behavioural tests makes zebrafish an excellent model for neurotoxicity studies. This review delves into the main experimental approaches adopted and the main markers analysed in neurotoxicity studies in zebrafish, showing that neurotoxic phenomena can be triggered not only by exposure to chemical substances but also by fluctuations in temperature. The findings presented here serve as a valuable resource for the study of neurotoxicity in zebrafish and define new scenarios in ecotoxicology suggesting that alterations in temperature can synergistically compound the neurotoxic effects of chemical substances, intensifying their detrimental impact on fish populations.

show abstract

“…Larval zebrafish have also been used to screen the behavioral effects of stress exposure, antidepressants, and genetic mutations [ 33 – 36 ]. However, few published studies have examined or discussed the possible behavioral effects of psychedelics in larval zebrafish [ 37 – 39 ], and, to date, there have been no reports on detailed behavioral effects of psilocybin. Such scarcity of behavioral insights impedes further research into their actions in neural circuit dynamics.…”

Section: Introductionmentioning

confidence: 99%

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

Braun,

Rosenberg,

Rabaniam

et al. 2024

Mol Psychiatry

View full text Add to dashboard Cite

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.

show abstract

Developmental Neurotoxicity Screen of Psychedelics and Other Drugs of Abuse in Larval Zebrafish (Danio rerio)

Cited by 7 publications

References 47 publications

The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits

The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits

Temperature- and chemical-induced neurotoxicity in zebrafish

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

Contact Info

Product

Resources

About