Original Investigation

Psychopharmacology

, 202:103

First online:

Nicotine effects on learning in zebrafish: the role of dopaminergic systems

  • Donnie EddinsAffiliated withDepartment of Psychiatry and Behavioral Sciences, Neurobehavioral Research Laboratory, Duke University Medical Center
  • , Ann PetroAffiliated withDepartment of Psychiatry and Behavioral Sciences, Neurobehavioral Research Laboratory, Duke University Medical Center
  • , Paul WilliamsAffiliated withDepartment of Psychiatry and Behavioral Sciences, Neurobehavioral Research Laboratory, Duke University Medical Center
  • , Daniel T. CeruttiAffiliated withDepartment of Psychiatry and Behavioral Sciences, Neurobehavioral Research Laboratory, Duke University Medical Center
  • , Edward D. LevinAffiliated withDepartment of Psychiatry and Behavioral Sciences, Neurobehavioral Research Laboratory, Duke University Medical Center Email author 

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Abstract

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.

Keywords

Nicotine Zebrafish Learning Dopamine DOPAC Spatial discrimination