There is a growing concern that exposure to environmental chemicals in early life may interfere with brain development. In particular, neonicotinoid pesticides have drawn considerable attention. As a pesticide class, neonicotinoids are designed to overstimulate insect nicotinic acetylcholine receptors (nAChRs). These pesticides were previously thought to be relatively harmless to mammalian species because of their low binding affinities to mammalian nAChRs. However, recent in vivo and in vitro studies have reported that neonicotinoids possess sufficient binding affinity and agonistic potential for mammalian nAChRs to exert nicotine-like effects that are stronger than originally believed. Neonicotinoids such as acetamiprid, imidacloprid, and clothianidin can bind to the α4 and β2 subunits of mammalian nAChRs. The α4β2 nAChRs are present in various brain regions such as the amygdala, hypothalamus, substantia nigra, ventral tegmental area, raphe nuclei, hippocampus, and medial habenula, and regulate the development and functions of these regions. These brain regions are involved in the regulation of socio-sexual behaviors, anxiety, depression, memory, and learning . Therefore, perinatal exposure to neonicotinoids is thought to impair specific behaviors by affecting the formation of neuronal circuits, including circuits involving these areas.
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.
Source:
Sano K et al. Front. Neurosci., 03 June 2016 | http://dx.doi.org/10.3389/fnins.2016.00228
http://journal.frontiersin.org/article/10.3389/fnins.2016.00228/full
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