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.