How do zebrafish (Danio rerio) respond to MK-801 and amphetamine? Relevance for assessing schizophrenia-related endophenotypes in alternative model organisms,Journal of Neuroscience Research

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How do zebrafish (Danio rerio) respond to MK-801 and amphetamine? Relevance for assessing schizophrenia-related endophenotypes in alternative model organisms
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2021-09-08 , DOI: 10.1002/jnr.24948
Radharani Benvenutti _{1,

2} , Matheus Gallas-Lopes ₁ , Adrieli Sachett _{1,

2} , Matheus Marcon _{1,

2} , Nathan Ryzewski Strogulski ₃ , Carlos Guilherme Reis _{1,

2} , Rafael Chitolina _{1,

2} , Angelo Piato _{1,

2,

4} , Ana Paula Herrmann _{1,

4}

Affiliation

Schizophrenia pathophysiology has been associated with dopaminergic hyperactivity, NMDA receptor hypofunction, and redox dysregulation. Most behavioral assays and animal models to study this condition were developed in rodents, leaving room for species-specific biases that could be avoided by cross-species approaches. As MK-801 and amphetamine are largely used in mice and rats to mimic schizophrenia features, this study aimed to compare the effects of these drugs in several zebrafish (Danio rerio) behavioral assays. Male and female adult zebrafish were exposed to MK-801 (1, 5, and 10 μM) or amphetamine (0.625, 2.5, and 10 mg/L) and observed in paradigms of locomotor activity and social behavior. Oxidative parameters were quantified in brain tissue. Our results demonstrate that MK-801 disrupted social interaction, an effect that resembles the negative symptoms of schizophrenia. It also altered locomotion in a context-dependent manner, with hyperactivity when fish were tested in the presence of social cues and hypoactivity when tested alone. On the other hand, exposure to amphetamine was devoid of effects on locomotion and social behavior, while it increased lipid peroxidation in the brain. Key outcomes induced by MK-801 in rodents, such as social interaction deficit and locomotor alterations, were replicated in zebrafish, corroborating previous studies and reinforcing the use of zebrafish to study schizophrenia-related endophenotypes. More studies are necessary to assess the predictive validity of preclinical paradigms with this species and ultimately optimize the screening of potential novel treatments.

中文翻译：

斑马鱼 (Danio rerio) 对 MK-801 和安非他明有何反应？评估替代模式生物中与精神分裂症相关的内表型的相关性

精神分裂症的病理生理学与多巴胺能亢进、NMDA 受体功能减退和氧化还原失调有关。大多数研究这种情况的行为分析和动物模型都是在啮齿动物中开发的，为物种特异性偏差留下了空间，这些偏差可以通过跨物种方法来避免。由于 MK-801 和安非他明主要用于小鼠和大鼠来模拟精神分裂症的特征，本研究旨在比较这些药物对几种斑马鱼 ( Danio rerio ) 的影响。) 行为分析。雄性和雌性成年斑马鱼暴露于 MK-801（1、5 和 10 μM）或苯丙胺（0.625、2.5 和 10 mg/L），并在运动活动和社会行为范式中观察到。在脑组织中量化氧化参数。我们的研究结果表明，MK-801 扰乱了社交互动，这种效果类似于精神分裂症的负面症状。它还以上下文相关的方式改变了运动，当鱼在存在社会线索的情况下进行测试时会出现过度活跃，而单独测试时会出现低活跃度。另一方面，接触安非他明对运动和社会行为没有影响，但会增加大脑中的脂质过氧化。MK-801 在啮齿动物中诱导的关键结果，例如社交互动缺陷和运动改变，在斑马鱼中得到了复制，证实以前的研究并加强使用斑马鱼来研究精神分裂症相关的内表型。需要更多的研究来评估该物种的临床前范式的预测有效性，并最终优化潜在新疗法的筛选。

更新日期：2021-09-08

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