Nicotine effects on learning in zebrafish: the role of dopaminergic systems
Nicotine effects on learning in zebrafish: the role of dopaminergic systems
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DOI：
10.1007/s00213-008-1287-4
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发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Levin, Edward D.
中科院分区：
文献类型：
--
作者：
Eddins, Donnie;Petro, Ann;Levin, Edward D.
尼古丁改善了许多动物模型的认知功能，包括大鼠，小鼠，猴子，最近，斑马鱼。斑马鱼模型允许更高的吞吐量和更容易发现认知改善的机制。为了进一步表征尼古丁对斑马鱼学习影响的神经基础，我们确定了伴随尼古丁增强学习的多巴胺能系统的变化。尼古丁改善了学习，并增加了大脑中主要多巴胺代谢物二羟基苯乙酸（DOPAC）的水平。选择准确性与DOPAC水平之间存在显著相关性。尼古丁拮抗剂美加明阻断了尼古丁诱导的DOPAC浓度的增加，这与我们先前发现的美加明逆转尼古丁诱导的学习改善相一致。多巴胺系统与斑马鱼的学习有关;尼古丁暴露增加了学习率和DOPAC水平;尼古丁拮抗剂给药阻断了尼古丁诱导的DOPAC浓度的升高。用斑马鱼对药物进行快速认知评估可以作为开发认知功能障碍新疗法的有用筛选工具。
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.To further characterize the neural bases of nicotine effects on learning in zebrafish, we determined changes in dopaminergic systems that accompany nicotine-enhanced learning.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.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.