4.7 Article

The effects of fipronil on emotional and cognitive behaviors in mammals

Journal

PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
Volume 175, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.pestbp.2021.104847

Keywords

Fipronil; Fipronil sulfone; Veterinary drugs; Mammal cognition; Mammal behavior

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [16H0177906, 18K1984708, 18KK028708, JPMXS0420100620, 17K2003807, 18H0413208, 17KK0009, 19H0427719, JP19K19406]
  2. foundation of JSPS Bilateral Open Partnership Joint Research Projects [JPJSBP120209902]
  3. Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan [SII-1/3-2, 4RF-1802/18949907]
  4. Soroptimist Japan Foundation
  5. Nakajima Foundation
  6. Sumitomo Foundation
  7. Nihon Seimei Foundation
  8. Japan Prize Foundation
  9. JST/JICA, SATREPS (Science and Technology Research Partnership for Sustainable Development) [JPMJSA1501]
  10. Hokkaido University School of Veterinary Medicine Wise/Leading Travel and Subsistence grant

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This study aimed to examine the pharmacokinetic profile of fipronil in mice, dogs, and cats, and evaluate its effects on emotional and cognitive behaviors of dogs and cats using data obtained from mice. The results showed that fipronil is distributed throughout the body of mice and metabolized primarily in the liver. Fipronil and its metabolite had longer half-lives in dogs and cats compared to mice.
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.

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