Long-term behavioral and neurochemical paradoxical alterations elicited following intranasal application of a chlorpyrifos formulation in mice.

The intranasal (IN) administration route represents a pathway for xenobiotics to reach the brain. The present study aimed to address the long-term consequences of IN administration of a chlorpyrifos (CPF) commercial formulation (fCPF) in mice. For this purpose, adult male CF-1 mice were intranasally administered with fCPF (10 mg/kg/day) three days a week, for 2 and 4 weeks, respectively. Behavioral and biochemical analyses were conducted 3-7, and 7.5 months after the last IN fCPF administration, respectively. Following a 6-month fCPF-free washout period, fur appearance and body injuries scores improved in the fCPF-treated groups. Notably, spatial learning and memory enhancement was observed 4 and 7 months after the last IN fCPF administration. Changes in oxidative stress markers and the activities of enzymes involved in cholinergic and glutamatergic pathways were observed in different brain areas from fCPF-treated mice, still after 7.5 months from fCPF application. Altogether, these neurochemical disturbances could be responsible for the described behavioral observations.

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Declaration of Competing Interest This research was supported by grants from the Secretaría General de Ciencia y Tecnología (UNS)PGI 24/B278 (CJB), PGI 24/B297 (CJB), PGI 24/B224 (CJB), PGI 24/ZB92 (CEG); CONICET Grant PIP 11220200102660CO (CJB); ANPCYT Grant PICT 2020 Serie A-00787 (CEG). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.