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Updated: Sep 29, 2025

Author Spotlight: Assessment of Environmental and Drug-Induced Behavioral Changes in Adult Zebrafish
Published on: November 3, 2023
Fluoxetine-induced neurotoxicity at environmentally relevant concentrations in adult zebrafish Danio rerio
José Manuel Orozco-Hernández1, Leobardo Manuel Gómez-Oliván1, Gustavo Axel Elizalde-Velázquez1
1Laboratorio de Toxicología Ambiental, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón intersección Paseo Tollocan, Colonia Residencial Colón, CP 50120 Toluca, Estado de México, Mexico.
Abstract:
Fluoxetine (FLX) exerts its therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin. Nonetheless, at high concentrations of this drug, adverse effects occur in the brain of exposed organisms. Bearing this into account, the objective of this study was to evaluate the neurotoxic effects of the fluoxetine through the evaluation of behavior (Novel tank test), determination of oxidative stress, and determination of acetylcholinesterase (AChE) activity in adult zebrafish Danio rerio. For this purpose, Danio rerio adults were exposed to three environmentally relevant concentrations (5, 10, 16 ng L-1) of FLX for 96 h. Our results demonstrate fish presented a significant disruption in their behavior, as they remained long-lasting time frozen at the top of the tank. Since we observed a significant reduction of AChE activity in the brain of fish, we believe the above described anxiety-like state is the result of this enzyme impairment. Moreover, as FLX-exposed fish showed a significant increase in the levels of oxidative damage biomarkers, we suggest this AChE disruption is associated with the oxidative stress response fish exhibited. Based on our findings, we believe the environmentally relevant concentration of FLX alters the redox status of the brain, impairing this way the behavior of fish and making them more vulnerable to predation.
Insights
Environmentally relevant concentrations of fluoxetine (FLX) cause neurotoxicity in zebrafish. This drug impairs acetylcholinesterase activity and increases oxidative stress, leading to behavioral changes and increased predation risk.
Area of Science:
- Environmental toxicology
- Neuroscience
- Zebrafish models
Background:
- Fluoxetine (FLX) is a selective serotonin reuptake inhibitor used therapeutically.
- High concentrations of FLX can cause adverse neurotoxic effects.
- Understanding FLX's impact on aquatic organisms is crucial for environmental safety.
Purpose of the Study:
- To evaluate the neurotoxic effects of environmentally relevant fluoxetine concentrations in adult zebrafish (Danio rerio).
- To assess behavioral changes, oxidative stress, and acetylcholinesterase (AChE) activity following FLX exposure.
Main Methods:
- Adult zebrafish were exposed to 5, 10, and 16 ng/L of FLX for 96 hours.
- Behavior was assessed using the Novel Tank Test.
- Oxidative stress biomarkers and AChE activity in the brain were measured.
Main Results:
- Zebrafish exhibited significant behavioral disruption, including prolonged freezing at the tank's top.
- A significant reduction in brain AChE activity was observed in FLX-exposed fish.
- Increased levels of oxidative damage biomarkers indicated a significant oxidative stress response.
Conclusions:
- Environmentally relevant concentrations of FLX alter the redox status in the zebrafish brain.
- Impaired AChE activity and oxidative stress contribute to anxiety-like behavior and increased vulnerability.
- FLX exposure poses a risk to aquatic wildlife by affecting behavior and survival.

