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Updated: Jul 13, 2025

Studying Neurobehavioral Effects of Environmental Pollutants on Zebrafish Larvae
Published on: February 5, 2020
Impact of environmentally relevant concentrations of fluoxetine on zebrafish larvae: From gene to behavior
Daniela Correia1, Marina Bellot2, Eva Prats3
1Centre for Environmental and Marine Studies (CESAM), Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Abstract:
Fluoxetine is widely prescribed for the treatment of depressive states, acting at the level of the central nervous system, consequently affecting non-target organisms. This study aimed to investigate the influence of environmentally relevant fluoxetine concentrations (1-1000 ng/L) on Danio rerio development, assessing both embryotoxicity and behavior, antioxidant defense, gene expression and neurotransmitter levels at larval stage. Exposure to fluoxetine during early development was found to be able to accelerate embryo hatching in embryos exposed to 1, 10 and 100 ng/L, reduce larval size in 1000 ng/L, and increase heart rate in 10, 100 and 1000 ng/L exposed larvae. Behavioral impairments (decreased startle response and increased larvae locomotor activity) were associated with effects on monoaminergic systems, detected through the downregulation of key genes (vmat2, mao, tph1a and th2). In addition, altered levels of neurochemicals belonging to the serotonergic and dopaminergic systems (increased levels of tryptophan and norepinephrine) highlighted the sensitivity of early life stages of zebrafish to low concentrations of fluoxetine, inducing effects that may compromise larval survival. The obtained data support the necessity to test low concentrations of SSRIs in environmental risk assessment and the use of biomarkers at different levels of biological organization for a better understanding of modes of action.
Insights
Environmentally relevant fluoxetine concentrations impact zebrafish development, causing altered hatching, growth, and behavior. These effects on monoaminergic systems highlight the need for assessing SSRIs in environmental risk evaluations.
Area of Science:
- Environmental toxicology
- Developmental biology
- Neuroscience
Background:
- Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is widely prescribed for depression.
- Its action on the central nervous system raises concerns about effects on non-target aquatic organisms.
Purpose of the Study:
- To investigate the impact of environmentally relevant fluoxetine concentrations (1-1000 ng/L) on zebrafish (Danio rerio) development.
- To assess embryotoxicity, behavioral changes, antioxidant defense, gene expression, and neurotransmitter levels in larval zebrafish.
Main Methods:
- Zebrafish embryos and larvae were exposed to varying concentrations of fluoxetine.
- Evaluated endpoints included hatching rate, larval size, heart rate, startle response, locomotor activity, gene expression (vmat2, mao, tph1a, th2), and neurotransmitter levels (tryptophan, norepinephrine).
Main Results:
- Fluoxetine exposure accelerated hatching at 1-100 ng/L, reduced larval size at 1000 ng/L, and increased heart rate across multiple concentrations.
- Behavioral impairments, including reduced startle response and increased locomotor activity, were observed.
- Downregulation of key genes in monoaminergic systems and altered neurotransmitter levels (tryptophan, norepinephrine) indicated neurochemical system sensitivity.
Conclusions:
- Early life stages of zebrafish are sensitive to low fluoxetine concentrations, with effects potentially compromising larval survival.
- Environmental risk assessments should include testing low SSRI concentrations.
- Biomarkers at various biological levels are crucial for understanding SSRI modes of action in aquatic ecosystems.

