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Stress-mediated hyperactivity and anhedonia resistant to diazepam and fluoxetine in drosophila
Stress ( IF 2.3 ) Pub Date : 2020-05-02 , DOI: 10.1080/10253890.2020.1759547
Ana Belén Ramos-Hryb 1, 2 , Mauro Federico Ramirez 1 , Cilene Lino-de-Oliveira 2, 3 , Mario Rafael Pagani 1
Affiliation  

Abstract

Distresses may induce behavioral phenotypes constituting heuristic models for psychopharmacology studies. In several species, including Drosophila, antidepressants counteract stress-induced phenotypes allowing the use of these models to test new psychoactive drugs. Here, we developed a novel and time-efficient protocol to provoke stress-induced phenotypes in Drosophila for the study of psychopharmacological agents. In the first experiment, flies (n = 12/groups) were exposed to a random-sequence of different types of stresses during nearly 24 h (including social isolation, fasting, heat, and electric shock), a protocol named short-term variable stress (SVS). Second, flies were exposed to a single stressful stimulus (social isolation, fasting, heat shock or electric shock, n = 12/groups). Next, flies submitted to SVS protocol were treated with vehicle, diazepam or fluoxetine (n = 12/groups). At the end of the stress protocols, behavioral phenotypes were evaluated in the open field (OF) and sucrose preference tests. In comparison to the unstressed group, flies exposed to SVS exhibited hyperactivity, as well as shorter times exploring the boundaries of the OF. In contrast to fasting stress, SVS reduced sucrose preference in flies. By analyzing the effects of individual stimuli on fly behavior, fasting and electric shock appear to be the predominant influences on the SVS-induced behaviors. Although fluoxetine or diazepam reduced the initial locomotor activity of flies, no treatment prevented the sequelae of SVS. Altogether, this study provides a time-efficient model system for the study of stress-mediated hyperactivity and anhedonia-like state resistant to fluoxetine and diazepam. The applications of SVS in Drosophila to preclinical psychopharmacology require further studies.

  • LAY SUMMARY
  • Exposition to unpredictable stress plays a significant role in psychiatric disorder’s onset. Behavioral traits of these disorders can be partially modeled in rodents aimed at developing psychopharmacological therapies. However, studies in rodents were questioned by ethical issues. Focused on 3Rs principles, we developed a preclinical model for stress and psychopharmacology research in Drosophila. Variable stress induced behavioral alterations, including hyperlocomotion and reduced preference for sucrose in flies. However, behavioral alterations were resistant to fluoxetine and diazepam.



中文翻译:

胁迫介导的果蝇对地西epa和氟西汀的抗性快感缺乏

摘要

困扰可能会诱发行为表型,构成用于心理药理学研究的启发式模型。在包括果蝇在内的多个物种,抗抑郁药可以抵消压力诱导的表型,从而允许使用这些模型来测试新型精神活性药物。在这里,我们开发了一种新颖且省时的方案,以激发果蝇中应激诱导的表型,用于研究心理药物。在第一个实验中,苍蝇(n = 12 /组)在将近24小时(包括社交隔离,禁食,热和电击)中随机暴露于不同类型的压力中,该协议称为短期可变压力(SVS)。其次,果蝇受到单一压力刺激(社交隔离,禁食,热休克或电击,n  = 12 /组)。接下来,将接受SVS方案检疫的果蝇用赋形剂,地西epa或氟西汀(n = 12 /组)。在压力实验方案结束时,在开放视野(OF)和蔗糖偏爱测试中评估行为表型。与未受压力的组相比,暴露于SVS的果蝇表现出活动过度,而且探索OF边界的时间更短。与空腹胁迫相反,SVS降低了果蝇中的蔗糖偏爱。通过分析个体刺激对飞行行为的影响,禁食和电击似乎是对SVS诱导行为的主要影响。尽管氟西汀或地西epa降低了果蝇的初始运动能力,但尚无治疗方法可预防SVS的后遗症。总而言之,这项研究为研究压力介导的过度活跃和对氟西汀和地西resistant的抗性类似快感状态提供了一个省时的模型系统。SVS的应用果蝇到临床前的心理药理学需要进一步的研究。

  • 图层摘要
  • 暴露于不可预测的压力在精神疾病的发作中起重要作用。这些疾病的行为特征可以在旨在开发心理药物疗法的啮齿动物中部分建模。但是,对啮齿类动物的研究受到伦理问题的质疑。我们专注于3Rs原理,为果蝇的压力和心理药理学研究开发了临床前模型。压力变化引起行为改变,包括过度运动和果蝇对蔗糖的偏好降低。但是,行为改变对氟西汀和地西epa具有抗性。

更新日期:2020-05-02
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