Sex-specific behavioral effects of acute exposure to the neonicotinoid clothianidin in mice

• Published in: Toxicology and applied pharmacology Vol. 456; p. 116283
• Main Authors: Kubo, Shizuka, Hirano, Tetsushi, Miyata, Yuka, Ohno, Shuji, Onaru, Kanoko, Ikenaka, Yoshinori, Nakayama, Shouta M.M., Ishizuka, Mayumi, Mantani, Youhei, Yokoyama, Toshifumi, Hoshi, Nobuhiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2022
• Subjects: Animals; Behavior; Clothianidin; Female; Guanidines - toxicity; Insecticides - toxicity; Learning Memory; Male; Mammals; Mice; Mice, Inbred C57BL; Neonicotinoid; Neonicotinoids - toxicity; Sex Difference; Neonicotinoid; Learning Memory; Sex Difference; Behavior; Clothianidin
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2022.116283

Although neonicotinoids are among the major classes of pesticides that affect mammalian nervous systems, little is known about sex differences in their effects. This study aimed to examine whether the neurobehavioral effects of a neonicotinoid, clothianidin (CLO), differed between sexes. Male and female C57BL/6N mice were orally administered CLO (5 or 50 mg/kg) at or below the chronic no-observed-adverse-effect-level (NOAEL) and subjected to behavioral tests of emotional and learning functions. Changes in neuroactivity in several brain regions and the concentrations of CLO and its metabolites in blood and urine were measured. Acute CLO exposure caused sex-related behavioral effects; decreases in locomotor activities and elevation of anxiety-like behaviors were more apparent in males than in females. In addition, male-specific impairment of short- and long-term learning memory by CLO exposure was observed in both the novel recognition test and the Barnes maze test. Male-dominant increases in the number of c-fos positive cells were observed in the paraventricular thalamic nucleus in the thalamus and in the dentate gyrus in the hippocampus, which are related to the stress response and learning function, respectively. The concentrations of CLO and most metabolites in blood and urine were higher in males. These results support the notion that male mice are more vulnerable than females to the neurobehavioral effects of CLO and provide novel insights into the risk assessment of neonicotinoids in mammalian neuronal function. •Sex-related differences in behavioral effects of clothianidin (CLO) were examined.•Male mice were more susceptible to behavioral effects of acute CLO than females.•Acute CLO impaired short and long term learning only in male mice.•Neuroactivities in thalamus and hippocampus increased in male-dominant manner.•Concentration of CLO and its metabolites were higher in male mice than females.