Theodoridi Antonia, Tsalafouta Aleka, Pavlidis Michail
Laboratory of Fish Physiology, Department of Biology, University of CreteHeraklion, Greece.
Front Neurosci. 2017 Apr 25;11:223. doi: 10.3389/fnins.2017.00223. eCollection 2017.
Zebrafish, , is an emerging model organism in stress and neurobehavioral studies. In nature, the species forms shoals, yet when kept in pairs it exhibits an agonistic and anxiety-like behavior that leads to the establishment of dominant-subordinate relationships. Fluoxetine, a selective serotonin reuptake inhibitor, is used as an anxiolytic tool to alter aggressive behavior in several vertebrates and as an antidepressant drug in humans. Pairs of male zebrafish were held overnight to develop dominant-subordinate behavior, either treated or non-treated for 2 h with fluoxetine (5 mg L), and allowed to interact once more for 1 h. Behavior was recorded both prior and after fluoxetine administration. At the end of the experiment, trunk and brain samples were also taken for cortisol determination and mRNA expression studies, respectively. Fluoxetine treatment significantly affected zebrafish behavior and the expression levels of several genes, by decreasing offensive aggression in dominants and by eliminating freezing in the subordinates. There was no statistically significant difference in whole-trunk cortisol concentrations between dominant and subordinate fish, while fluoxetine treatment resulted in higher ( = 0.004) cortisol concentrations in both groups. There were statistically significant differences between dominant and subordinate fish in brain mRNA expression levels of genes involved in stress axis (), neural activity (, ), and the serotonergic system (). The significant decrease in the offensive and defensive aggression following fluoxetine treatment was concomitant with a reversed pattern in expression levels. Overall, an acute administration of a selective serotonin reuptake inhibitor alters aggressive behavior in male zebrafish in association with changes in the neuroendocrine mediators of coping styles.
斑马鱼是应激和神经行为研究中一种新兴的模式生物。在自然环境中，该物种会形成鱼群，但当成对饲养时，它会表现出争斗和类似焦虑的行为，从而导致建立主导-从属关系。氟西汀是一种选择性5-羟色胺再摄取抑制剂，在几种脊椎动物中用作改变攻击行为的抗焦虑工具，在人类中用作抗抑郁药物。将雄性斑马鱼成对饲养过夜以形成主导-从属行为，用氟西汀（5毫克/升）处理或不处理2小时，然后再让它们相互作用1小时。在给予氟西汀之前和之后都记录行为。在实验结束时，还分别采集躯干和脑样本用于测定皮质醇和进行mRNA表达研究。氟西汀处理显著影响斑马鱼的行为和几个基因的表达水平，减少了主导鱼的攻击性攻击，并消除了从属鱼的僵住行为。主导鱼和从属鱼的全躯干皮质醇浓度没有统计学上的显著差异，而氟西汀处理导致两组的皮质醇浓度都更高（P = 0.004）。主导鱼和从属鱼在参与应激轴（）、神经活动（，）和5-羟色胺能系统（）的基因的脑mRNA表达水平上存在统计学上的显著差异。氟西汀处理后攻击性和防御性攻击的显著降低与表达水平的反向模式相伴。总体而言，急性给予选择性5-羟色胺再摄取抑制剂会改变雄性斑马鱼的攻击行为，并伴随着应对方式的神经内分泌介质的变化。
