Aging-related changes in the sensitivity of behavioral effects of the neonicotinoid pesticide clothianidin in male mice

• Published in: Toxicology letters Vol. 342; pp. 95 - 103
• Main Authors: Hirano, Tetsushi, Miyata, Yuka, Kubo, Shizuka, Ohno, Shuji, Onaru, Kanoko, Maeda, Mizuki, Kitauchi, Sayaka, Nishi, Misaki, Tabuchi, Yoshiaki, Ikenaka, Yoshinori, Ichise, Takahiro, Nakayama, Shouta M.M., Ishizuka, Mayumi, Arizono, Koji, Takahashi, Keisuke, Kato, Keisuke, Mantani, Youhei, Yokoyama, Toshifumi, Hoshi, Nobuhiko
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-05-2021
• Subjects: Aging; Animals; Behavior, Animal - drug effects; Behavioral test; Clothianidin; Dose-Response Relationship, Drug; Guanidines - administration & dosage; Guanidines - toxicity; Insecticides - administration & dosage; Insecticides - toxicity; Male; Mice; Mice, Inbred C57BL; Neonicotinoid; Neonicotinoids - administration & dosage; Neonicotinoids - toxicity; Thiazoles - administration & dosage; Thiazoles - toxicity; Tissue accumulation; Aging; Neonicotinoid; Behavioral test; Tissue accumulation; Clothianidin
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2021.02.010

•Behavioral effects of neonicotinoid pesticide clothianidin were compared in adult and aging mice.•A sub-NOAEL level of clothianidin decreased the locomotor activity in some behavioral tests in the aging mice, but not in the adult mice.•The concentrations of most CLO and its metabolites were higher in the blood and brain in the aging group than the adult group.•These results suggested age-related differences in the adverse effects of neonicotinoids in mammals.
Neonicotinoids, which act as agonists of the nicotinic acetylcholine receptors of insects, are widely used pesticides worldwide. Although epidemiological studies revealed that the detection amounts of neonicotinoids in urine are higher in the elderly population than other age-groups, there is no available information regarding the risks of neonicotinoids to older mammals. This study was aimed to investigate aging-related differences in the behavioral effects of the neonicotinoid pesticide clothianidin (CLO). We acutely administered a sub-NOAEL level (5 mg/kg) of CLO to adult (12-week-old) and aging (90-week-old) mice and conducted four behavioral tests focusing on the emotional behavior. In addition, we measured the concentrations of CLO and its metabolites in blood, brain and urine. There were age-related changes in most parameters in all behavioral tests, and CLO significantly decreased the locomotor activity in the open field test and elevated plus-maze test in the aging group, but not in the adult group. The concentrations of most CLO and its metabolites were significantly higher in the blood and brain and were slightly lower in the urine in the aging group compared to the adult group. These findings should contribute to our understanding of age-related differences in the adverse effects of neonicotinoids in mammals.