Peripubertal exposure to the neonicotinoid pesticide dinotefuran affects dopaminergic neurons and causes hyperactivity in male mice

Abstract

Although neonicotinoid pesticides are expected to have harmful influence on mammals, there is little animal experimental data to support the effect and mechanisms. Since acetylcholine causes the release of dopamine, neonicotinoids may confer a risk of developmental disorders via a disturbance in the monoamine systems. Male mice were peripubertally administered dinotefuran (DIN) referring to no observed effect level (NOEL) and performed behavioral and immunohistological analyses. In an open field test, the total locomotor activity was increased in a dose-dependent manner. The immunoreactivity of tyrosine hydroxylase in the substantia nigra was increased in DIN-exposed mice. These results suggest that exposure to DIN in peripubertal male mice causes hyperactivity and a disturbance of dopaminergic signaling.

Immunotoxicity evaluation by subchronic oral administration of clothianidin in Sprague-Dawley rats

“…However, several studies have reported the disappearance and mass death of honeybees in Europe, as well as in America and other countries, occurring since the 1990s [18,21,65], which has raised concerns about the secondary effects of these agents on non-targeted insects. It has also recently been reported that NNs have adverse effects on vertebrates for example, on the reproductive organs in reptiles [9], birds [26,60] and mammals [67], and the emotional behavior in mice [23,24,59,68]. In order to assess the risk of NNs, therefore, there is an urgent need for definitive information about their effects on mammals.…”

Fetal and lactational exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid pesticide clothianidin inhibits neurogenesis and induces different behavioral abnormalities at the developmental stages in male mice

“…NNs have a higher affinity for insect nicotinic acetylcholine receptors (nAChRs) than mammal nAChRs [ 29 ] and were originally considered safe for mammals. However, in the last decade it has been reported that NNs have nicotine-like excitatory effects on mammalian nAChRs [ 13 ], especially clothianidin (CLO), a type of NN, has been reported to be toxic to mammalian emotional behavior even at less than the no-observed-adverse-effect level (NOAEL) [ 8 , 9 , 26 , 27 , 33 ]. Recent studies have also reported that NNs were detected in the urine and breast milk of pregnant women and newborns [ 2 , 10 , 15 ], and Ohno et al .…”

Effects of <i>in utero</i> and lactational exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid clothianidin on the reproductive organs of female mice

“…NNs bind more readily to insect nAChRs than to mammalian nAChRs [ 38 ]. However, recent studies have reported reproductive toxicity [ 15 ] and neurobehavioral effects [ 16 , 34 , 35 , 45 ] in mammals. In terms of reproductive toxicity, it has been shown that the NN clothianidin (CLO), causes the DNA fragmentation of germ cells and the inhibition of embryonic development in mature quail [ 18 , 19 , 37 ].…”