关键词: Anxiety-like behavior Clomipramine Cortisol Novel tank test Serotonin Serotonin syndrome Stress Surfacing Tricyclic antidepressant Zebrafish

Mesh : Animals Zebrafish Clomipramine / pharmacology administration & dosage Behavior, Animal / drug effects Hydrocortisone / metabolism Dose-Response Relationship, Drug Male Female Antidepressive Agents, Tricyclic / pharmacology administration & dosage Selective Serotonin Reuptake Inhibitors / pharmacology administration & dosage

来  源:   DOI:10.7717/peerj.17803   PDF(Pubmed)

Abstract:
Chronic treatment with clomipramine, a tricyclic antidepressant drug, reduces symptoms of obsessive-compulsive disorder (OCD) and can influence the activity of the hypothalamic-pituitary-adrenal axis. However, little is known regarding the effects of acute clomipramine on the immediate expression of stress responses. Serotonergic drugs can elicit surfacing, a behavioral profile potentially related to toxicity in fish, although surfacing has not yet been observed after clomipramine exposure. The present study investigated the impact of acute exposure to clomipramine on basal and stress-induced behaviors in the novel tank test and cortisol levels in mixed-sex, wild-type, adult zebrafish (Danio rerio). The findings show clomipramine-exposed groups (regardless of stress exposure) spent much more time in the top of the novel tank and had significantly less overall motor activity in the behavioral task compared to the fish not exposed to the drug. Then, the dose-dependent effects of acute clomipramine on activity in the surface of the novel tank (top third of the top half) were investigated further. Clomipramine dose-dependently increased surface-dwelling and elicited a dose-dependent hypoactivity in overall motor behavior. There were no statistically significant differences in whole-body cortisol levels in either experiment. Like other serotonin-acting drugs, clomipramine strongly elicited surface-dwelling and depressed motor behavior in adult zebrafish. Additional testing is needed to elucidate whether surfacing represents a toxic state and how serotonin regulates surfacing.
摘要:
氯米帕明的慢性治疗,一种三环抗抑郁药,减轻强迫症(OCD)的症状,并可以影响下丘脑-垂体-肾上腺轴的活动。然而,关于急性氯米帕明对应激反应的即时表达的影响知之甚少。5-羟色胺能药物可以引起表面,可能与鱼类毒性有关的行为概况,尽管在氯米帕明暴露后尚未观察到表面处理。本研究调查了在新型坦克试验中急性暴露于氯米帕明对基础和应激诱导行为的影响以及混合性中的皮质醇水平,野生型,成年斑马鱼(Daniorerio)。研究结果表明,与未暴露于药物的鱼相比,暴露于氯米帕明的组(无论压力暴露如何)在新型水箱顶部花费了更多的时间,并且在行为任务中的整体运动活动明显减少。然后,进一步研究了急性氯米帕明对新型储罐表面(上半部分的前三分之一)活性的剂量依赖性影响。氯米帕明剂量依赖性地增加了表面滞留,并引起了整体运动行为的剂量依赖性活动不足。在任一实验中,全身皮质醇水平均无统计学差异。像其他5-羟色胺药物一样,氯米帕明强烈引起成年斑马鱼的表面居住和运动行为抑郁。需要额外的测试来阐明表面处理是否代表毒性状态以及血清素如何调节表面处理。
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