Nicotine effects on learning in zebrafish: the role of dopaminergic systems.
RATIONALE: Nicotine improves cognitive function in a number of animal models including rats, mice, monkeys, and recently, zebrafish. The zebrafish model allows higher throughput and ease in discovering mechanisms of cognitive improvement. MATERIALS AND METHODS: To further characterize the neural bases of nicotine effects on learning in zebrafish, we determined changes in dopaminergic systems that accompany nicotine-enhanced learning. RESULTS: Nicotine improved learning and increased brain levels of dihydroxyphenylacetic acid (DOPAC), the primary dopamine metabolite. There was a significant correlation between choice accuracy and DOPAC levels. The nicotinic antagonist mecamylamine blocked the nicotine-induced increase in DOPAC concentrations, in line with our previous finding that mecamylamine reversed nicotine-induced learning improvement. CONCLUSIONS: Dopamine systems are related to learning in zebrafish; nicotine exposure increases both learning rates and DOPAC levels; and nicotinic antagonist administration blocks nicotine-induced rises in DOPAC concentrations. Rapid cognitive assessment of drugs with zebrafish could serve as a useful screening tool for the development of new therapeutics for cognitive dysfunction.
Eddins, D; Petro, A; Williams, P; Cerutti, DT; Levin, ED
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