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Updated: Aug 24, 2025

Small Molecule Screening and Toxicity Testing in Early-stage Zebrafish Larvae

Small Molecule Screening and Toxicity Testing in Early-stage Zebrafish Larvae

Published on: March 7, 2025

Methamphetamine-induced lethal toxicity in zebrafish larvae.

Yu Chen^1,2, Alexander S Wisner¹, Isaac T Schiefer^3,4

¹Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, 3000 Arlington Ave., MS 1015, Toledo, OH, 43614-2598, USA.

Psychopharmacology

|October 21, 2022

Summary

This summary is machine-generated.

Methamphetamine (METH) causes dose-dependent lethality in zebrafish larvae, affecting heart rate and causing seizures. Glutamatergic and dopaminergic systems are implicated in METH toxicity, offering a new screening method for novel psychoactive substances.

Keywords:

Ammonia Dopaminergic receptors Glutamate Heart Methamphetamine Seizure Zebrafish

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Area of Science:

Pharmacology
Toxicology
Neuroscience

Background:

Novel psychoactive substance use is increasing.
Rapid emergence of new substances necessitates efficient toxicity screening.
Zebrafish are a suitable model for high-throughput drug screening.

Purpose of the Study:

Investigate acute toxicity of methamphetamine (METH) in zebrafish larvae.
Elucidate mechanisms of METH toxicity.
Establish a high-throughput screening method for new psychoactive substances.

Main Methods:

Used 5-day post-fertilization (5 dpf) zebrafish larvae.
Examined METH lethality and toxicity across concentrations in a 96-well plate format.
Assessed effects of receptor antagonists (GYKI-52466, raclopride) on METH lethality.

Main Results:

METH induced dose-dependent lethality and cardiotoxicity (heart rate changes, decreased function).
Observed increased ammonia excretion, decreased internal ammonia, and seizures.
Glutamatergic and dopaminergic antagonists attenuated METH-induced lethality.

Conclusions:

Provides a baseline for studying amphetamine-related compound toxicity in zebrafish.
Establishes a high-throughput approach for novel psychoactive substance toxicity assessment.
Highlights the role of glutamatergic and dopaminergic systems in METH toxicity.