The effects of fipronil on emotional and cognitive behaviors in mammals
The effects of fipronil on emotional and cognitive behaviors in mammals
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DOI：
10.1016/j.pestbp.2021.104847
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发表时间：
2021-05-13
影响因子：
4.7
通讯作者：
Ikenaka, Yoshinori
中科院分区：
文献类型：
--
作者：
Suzuki, Tomohiro;Hirai, Anri;Ikenaka, Yoshinori
氟虫腈是一种苯吡唑类杀虫剂，被广泛用作杀虫剂和兽药，尽管研究表明它可能对哺乳动物有毒。本研究的目的是研究氟虫腈在小鼠、狗和猫体内的药代动力学特征，并利用从小鼠身上获得的数据评估其对狗和猫的情绪和认知行为的影响。对氟虫腈在小鼠和犬的体内动力学进行了评价。我们还进行了行为测试（升高的正迷宫和y迷宫），并测量了暴露于氟虫腈的小鼠的神经递质水平。此外，利用大鼠、小鼠、狗和猫的肝微粒体评估氟虫腈的体外代谢。结果表明，氟虫腈经皮肤施用后分布于小鼠全身（血液、脑、脂肪组织和肝脏）。它主要在肝脏代谢为氟虫腈砜。动力学数据表明氟虫腈和氟虫腈砜在狗和猫体内的半衰期都比在老鼠体内的半衰期长。行为测试表明，氟虫腈和氟虫腈砜可以影响小鼠的情绪和认知行为，并改变神经递质（纹状体中的多巴胺和海马中的血清素）的水平。此外，我们发现狗和猫的氟虫腈代谢能力比小鼠和大鼠低。然而，需要进一步的综合研究来确定氟虫腈是否会影响狗和猫的情绪和认知行为。据我们所知，这是第一次利用从老鼠身上获得的数据来检查药代动力学数据并验证氟虫腈对狗和猫的情感和认知行为的影响的研究。
Fipronil is a phenylpyrazole insecticide that is widely used as a pesticide and a veterinary drug, although studies suggest that it could be toxic to mammals. The objectives of this study were to examine the pharmacokinetic profile of fipronil in mice, dogs, and cats, and to evaluate its effects on emotional and cognitive behaviors of dogs and cats using the data obtained from mice. The assessment of in vivo kinetics of fipronil was conducted in mice and dogs. We also performed behavioral tests (elevated plus-maze and Y-maze) and measured the levels of neurotransmitters in mice exposed to fipronil. In addition, the in vitro metabolism of fipronil were evaluated using liver microsomes of rats, mice, dogs, and cats. The results revealed that fipronil is distributed throughout the body (blood, brain, adipose tissue, and liver) of mice after dermal application. It was metabolized to fipronil sulfone primarily in the liver. The data on kinetics show that both fipronil and fipronil sulfone have a longer halflife in dogs and cats than in mice. The behavioral tests indicated that fipronil and fipronil sulfone could affect emotional and cognitive behaviors and alter the levels of neurotransmitters (dopamine in the striatum and serotonin in the hippocampus) in mice. Furthermore, we found that dogs and cats have a low ability to metabolize fipronil than mice and rats. However, further comprehensive studies are needed to determine whether fipronil affects the emotional and cognitive behaviors when administered to dogs and cats. To the best of our knowledge, this is the first study to examine the pharmacokinetic data and verify the effects of fipronil on emotional and cognitive behaviors of dogs and cats using the data obtained from mice.