The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice

Tetsushi Hirano, Shogo Yanai, Takuya Omotehara, Rie Hashimoto, Yuria Umemura, Naoto Kubota, Kiichi Minami, Daichi Nagahara, Eiko Matsuo, Yoshiko Aihara, Ryota Shinohara, Tomoyuki Furuyashiki, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)


Neonicotinoids, some of the most widely used pesticides in the world, act as agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death from abnormal excitability. Neonicotinoids unexpectedly became a major topic as a compelling cause of honeybee colony collapse disorder, which is damaging crop production that requires pollination worldwide. Mammal nAChRs appear to have a certain affinity for neonicotinoids with lower levels than those of insects; there is thus rising concern about unpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids would be enhanced under a chronic stressed condition, which is known to alter the expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male mice actively administered a neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day), for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field test, although the locomotor activities were not affected, the anxiety-like behaviors of the mice were elevated by both CTD and stress. The present study demonstrates that the behavioral and reproductive effects of CTD become more serious in combination with environmental stress, which may reflect our actual situation of multiple exposure.

Original languageEnglish
Pages (from-to)1207-1215
Number of pages9
JournalJournal of Veterinary Medical Science
Issue number10
Publication statusPublished - Nov 5 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Veterinary


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