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

Abstract

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.

Effects of neonicotinoids on putative escape behavior of juvenile wood frogs (Lithobates sylvaticus) chronically exposed as tadpoles

“…Similar significant behavioral effects were detected with exposure to nicotine (Crosby et al 2015). Other studies using mice have also found effects on anxiety behaviors with exposure to clothianidin or acetamiprid, but in these studies anxiety was either increased (Hirano et al 2015) or decreased (Sano et al 2016). It is possible that the frogs may be highly anxious and resort to the preferred cryptic response instead of the less preferred flight response or have reduced anxiety and thus do not feel the need to flee.…”

Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

“…However, increasing evidence to the contrary [11,12,13,14,15,16,17,18,19], and consideration of some neonicotinoid metabolites showing high affinities for mammalian nAChRs [3], suggests that neonicotinoids have potential developmental neurotoxicity.…”

“…Furthermore, the neonicotinoids thiamethoxam and clothianidin induced dopamine release in the rat striatum via nAChRs [12] and thiamethoxam altered behavioral and biochemical processes related to the cholinergic systems in rat [13]. Gestational administration of clothianidin induces behavioral disorders in F1 mice [14] and exposure to clothianidin and other stress causes behavioral and reproductive abnormalities in male mice [15]. Exposure to IMI alters learning performance and related gene expression in infant and adult rats [16].…”

Non-target toxicity of novel insecticides

“…Exposure of gestating mice to clothianidin also reduced germ cell count in the offspring without hormonal changes (126). Still in mice, Hirano et al (127) reported clothianidin-induced behavioural and reproductive effects, which were more pronounced under chronic stress. Treatment of mouse embryos with 1000 µmol L -1 of thimaetoxam, clothianidin, acetamiprid, and thiacloprid during the preimplantation period had negative effects on embryo developmental abilities (128).…”