Parker Matthew O, Brock Alistair J, Sudwarts Ari, Teh Muy-Teck, Combe Fraser J, Brennan Caroline H
School of Biological and Chemical Sciences, Queen Mary University of London London, UK ; School of Health Sciences and Social Work, University of Portsmouth Portsmouth, UK.
School of Biological and Chemical Sciences, Queen Mary University of London London, UK.
Front Behav Neurosci. 2015 Oct 16;9:271. doi: 10.3389/fnbeh.2015.00271. eCollection 2015.
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 (ache (sb55/+)) 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) ache (sb55/+) revealed significant downregulation of chrna2, chrna5, and drd2 mRNA in ache (sb55/+) 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.
冲动是许多神经精神疾病的关键行为组成部分，介导个体冲动性差异的细胞和分子过程目前仍知之甚少。乙酰胆碱酯酶（ache）无义突变的杂合子斑马鱼（ache(sb55/+)）在五选择连续反应时任务（5-CSRTT）中表现出比野生型和ache(+/+)更低的冲动水平。对成年和幼体（9天龄）ache(sb55/+)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，ache(sb55/+)幼体中chrna2、chrna5和drd2 mRNA显著下调，但在成体中无差异。急性暴露于胆碱能激动剂/拮抗剂对冲动性没有影响，这支持了以下假设：在成体中观察到的行为效应是由于胆碱能和多巴胺能信号发育改变的持久影响。这显示了胆碱能信号在大脑发育过程中对冲动性的跨物种作用，并表明斑马鱼可能是胆碱能通路作为成瘾医学治疗进展靶点作用的有用模型。
