Long-Term Exposure to SSRI Citalopram Induces Neurotoxic Effects in Zebrafish

Area of Science:

• Environmental Toxicology
• Neuroscience
• Aquatic Ecotoxicology

Background:

• Residual antidepressants in aquatic environments pose risks to non-target organisms.
• Limited data exists on the long-term neurotoxic effects of antidepressants on aquatic wildlife.

Purpose of the Study:

• Investigate long-term citalopram neurotoxicity in zebrafish across two generations.
• Assess impacts on motor function, learning, and memory.
• Explore the reversibility of observed effects.

Main Methods:

• Long-term exposure of zebrafish (0-150 days postfertilization) to citalopram (0.1-100 μg/L).
• Behavioral assessments of motor function, learning, and memory.
• Whole-mount immunofluorescence assays to examine neuronal changes.
• Analysis of specific neuronal populations (serotonergic, cholinergic, glutamatergic, dopaminergic).

Main Results:

• Second-generation larvae (F1+) showed reduced sensorimotor performance at 100 μg/L citalopram, which was reversible upon transfer to clean water.
• Adult zebrafish (F0+) exposed long-term exhibited male-specific declines in motor, learning, and memory.
• Decreased glutamatergic spinal motor neurons and dopaminergic neurons were observed in exposed adults.
• No significant changes in serotonergic/cholinergic motor neurons or adult telencephalon neuronal apoptosis.

Conclusions:

• Long-term citalopram exposure induces multi-generational neurobehavioral effects in zebrafish.
• Neurotoxic mechanisms involve alterations in specific neuronal populations, particularly glutamatergic and dopaminergic neurons.
• Findings highlight potential environmental and health risks of antidepressant residues.