| Abstract: | Neonicotinoids, some of the most widely used pesticides in the world, act as agonists tothe nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death fromabnormal excitability. Neonicotinoids unexpectedly became a major topic as a compellingcause of honeybee colony collapse disorder, which is damaging crop production thatrequires pollination worldwide. Mammal nAChRs appear to have a certain affinity forneonicotinoids with lower levels than those of insects; there is thus rising concern aboutunpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that theeffects of neonicotinoids would be enhanced under a chronic stressed condition, which isknown to alter the expression of targets of neonicotinoids, i.e.,neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male miceactively administered a neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day),for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferousepithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathioneperoxidase 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 themice were elevated by both CTD and stress. The present study demonstrates that thebehavioral and reproductive effects of CTD become more serious in combination withenvironmental stress, which may reflect our actual situation of multiple exposure. |
