Developmental role of acetylcholinesterase in impulse control in zebrafish.
Developmental role of acetylcholinesterase in impulse control in zebrafish.
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DOI：
10.3389/fnbeh.2015.00271
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发表时间：
2015
影响因子：
3
通讯作者：
Brennan CH
中科院分区：
文献类型：
--
作者：
Parker MO;Brock AJ;Sudwarts A;Teh MT;Combe FJ;Brennan CH
人们对冲动个体差异的细胞和分子过程知之甚少，而冲动是许多神经精神疾病的关键行为组成部分。疼痛无义突变杂合子斑马鱼 (achesb55/+) 在 5 选择系列反应时间任务 (5-CSRTT) 中表现出比野生型和 ache+∕+ 更低的冲动水平。对成虫和幼虫 (9 dpf) achesb55/+ 中胆碱能 (nAChR)、血清素能 (5-HT) 和多巴胺 (DR) 受体 mRNA 表达的评估显示，achesb55/+ 幼虫中 chrna2、chrna5 和 drd2 mRNA 显着下调，但成虫中没有差异。急性暴露于胆碱能激动剂/拮抗剂对冲动没有影响，这支持了这样的假设：在成人中观察到的行为影响是由于胆碱能和多巴胺能信号的发育改变的持久影响。这表明胆碱能信号在大脑冲动发育过程中的跨物种作用，并表明斑马鱼可能是胆碱能通路作为成瘾医学治疗进展目标的有用模型。
Cellular and molecular processes that mediate individual variability in impulsivity, a key behavioral component of many neuropsychiatric disorders, are poorly understood. Zebrafish heterozygous for a nonsense mutation in ache (achesb55/+) showed lower levels of impulsivity in a 5-choice serial reaction time task (5-CSRTT) than wild type and ache+∕+. Assessment of expression of cholinergic (nAChR), serotonergic (5-HT), and dopamine (DR) receptor mRNA in both adult and larval (9 dpf) achesb55/+ revealed significant downregulation of chrna2, chrna5, and drd2 mRNA in achesb55/+ larvae, but no differences in adults. Acute exposure to cholinergic agonist/antagonists had no effect on impulsivity, supporting the hypothesis that behavioral effects observed in adults were due to lasting impact of developmental alterations in cholinergic and dopaminergic signaling. This shows the cross-species role of cholinergic signaling during brain development in impulsivity, and suggests zebrafish may be a useful model for the role of cholinergic pathways as a target for therapeutic advances in addiction medicine.