Neurotoxicity and behavioral disorders induced in mice by acute exposure to the diamide insecticide chlorantraniliprole

Diamide insecticides activate ryanodine receptors expressed in lepidopteran skeletal muscle and promote Ca2+ release in the sarcoplasmic reticulum, causing abnormal contractions and paralysis, leading to death of the pest. Although they had been thought not to act on nontarget organisms, including m...

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Bibliographic Details
Published in:Journal of Veterinary Medical Science 2023, pp.23-0041
Main Authors: KIMURA, Mako, SHODA, Asuka, MURATA, Midori, HARA, Yukako, YONOICHI, Sakura, ISHIDA, Yuya, MANTANI, Youhei, YOKOYAMA, Toshifumi, HIRANO, Tetsushi, IKENAKA, Yoshinori, HOSHI, Nobuhiko
Format: Article
Language:English
Subjects:
Animals
Anxiety
anxiety-like behavior
c-Fos protein
Calcium (reticular)
chlorantraniliprole
Corticosterone
Dentate gyrus
Diamide - toxicity
diamide insecticides
Hippocampus
Humans
Insecticides
Insecticides - toxicity
Mammals
Mice
monoamine neurotransmitters
Neonicotinoids
neurobehavioral toxicity
Neurotoxicity
Nontarget organisms
Paralysis
Ryanodine receptors
Sarcoplasmic reticulum
Skeletal muscle
Toxicology
Vocalization behavior
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Summary:Diamide insecticides activate ryanodine receptors expressed in lepidopteran skeletal muscle and promote Ca2+ release in the sarcoplasmic reticulum, causing abnormal contractions and paralysis, leading to death of the pest. Although they had been thought not to act on nontarget organisms, including mammals, adverse effects on vertebrates were recently reported, raising concerns about their safety in humans. We investigated the neurotoxicity of the acute no-observed-adverse-effect level of chlorantraniliprole (CAP), a diamide insecticide, in mice using clothianidin (CLO), a neonicotinoid insecticide, as a positive control. The CLO-administered group showed decreased locomotor activities, increased anxiety-like behaviors, and abnormal human-audible vocalizations, while the CAP-administered group showed anxiety-like behaviors but no change in locomotor activities. The CAP-administered group had greater numbers of c-fos‒immunoreactive cells in the hippocampal dentate gyrus, and similar to the results in a CLO-administered group in our previous study. Blood corticosterone levels increased in the CLO-administered group but did not change in the CAP-administered group. Additionally, CAP was found to decreased 3-Methoxytyramine and histamine in mice at the time to maximum concentration. These results suggest that CAP-administered mice are less vulnerable to stress than CLO-administered mice, and the first evidence that CAP exposure increases neuronal activity and induces anxiety-like behavior as well as neurotransmitter disturbances in mammals.
ISSN:0916-7250
1347-7439
DOI:10.1292/jvms.23-0041