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Methamphetamine-induced lethal toxicity in zebrafish larvae
Yu Chen1,2, Alexander S Wisner1, Isaac T Schiefer3,4
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
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.
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.
