In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

Abstract

Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically.

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.…”

“…Exposure to IMI alters learning performance and related gene expression in infant and adult rats [16]. Recently, Sano et al reported that exposure to low dose ACE in utero and through lactation induces abnormalities in socio-sexual and anxiety-related behaviors in male mice [17]. Additionally, an in vivo mouse study revealed that four types of neonicotinoids (ACE, IMI, thiacloprid, and nitenpyram) readily pass through the blood–brain barrier (BBB) and are detectable in the brain at 60%–70% of the serum concentration within 15 min of intraperitoneal administration [18].…”

Estrogenic action by tris(2,6-dimethylphenyl) phosphate, an impurity in resorcinol bis[di(2,6-dimethylphenyl) phosphate] flame retardant formulations, impairs the development of female reproductive functions

“…At the beginning of the trial, the mouse was introduced in the dark compartment. The latency to enter the light compartment and the cumulative time spent in the light compartment were measured by an automated video tracking system (ANY-maze, Stoelting, USA) (Sano et al, 2016).…”

“…Three trials were performed, each lasting 30 min. The number of attempted mounts, mounts, and intromissions was scored for each mouse (Sano et al, 2016).…”