Acute Modafinil Exposure Induces Neurobehavioral Alterations in Zebrafish: Implications for Off-Label Cognitive...

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Modafinil is prescribed for sleep disorders but is increasingly used off-label by neurotypical individuals as a cognitive enhancer.
• The neurological risks of modafinil's unsupervised use in healthy individuals are not well understood.

Purpose of the Study:

• To assess the toxicity and neurobehavioral effects of off-label modafinil exposure in neurotypical individuals using a zebrafish model.
• To investigate the impact of modafinil on behavior and key biochemical markers.

Main Methods:

• Zebrafish were exposed to varying concentrations of modafinil (200, 400, 600 mg/L) or a control (0 mg/L).
• Neurobehavioral assessments included novel tank, social preference, light-dark, forced swimming, and Y-maze tests.
• Biochemical analyses measured cortisol, nonprotein thiols, total protein, lipid peroxidation, and mitochondrial complex activity.

Main Results:

• Modafinil exposure induced significant neurobehavioral changes: hyperlocomotion, enhanced endurance, and anxiogenic-like behavior.
• Biochemical analysis showed increased total protein at high concentrations and increased lipid peroxidation at the lowest concentration.
• Cortisol levels, nonprotein thiols, and mitochondrial complex activity remained unchanged.

Conclusions:

• Acute modafinil exposure causes significant neurobehavioral alterations in zebrafish.
• Unsupervised cognitive enhancement with modafinil may pose substantial neurological risks for neurotypical individuals.