Repeated exposure to chlorpyrifos results in impaired sustained attention and increased impulsivity in rats.

Abstract

Introduction: Organophosphates such as chlorpyrifos remain in heavy use in the US and across the globe. Likelihood of unintentional subacute exposure to organophosphates is of great concern for populations that live within rural farming communities. Risk of exposure is highly dependent on pesticide dispersion and proximity to use and has the potential to contaminate the food and water supply. It is well documented that acute exposure to chlorpyrifos can cause cognitive deficits; however, the long-term effects are not well understood. Therefore, the aim of this study was to determine if repeated low-level exposure to chlorpyrifos impaired performance in an animal model of sustained attention.Methods: Adult male Wistar rats were food restricted to approximately 85% of their age-dependent, free-feeding weights based upon Harlan Laboratories growth rate curves. After one week of food restriction animals began training on the 5-choice serial reaction time task (5C-SRTT). Upon stable responding animals were treated with vehicle or chlorpyrifos 18.0 mg/kg daily for 14 consecutive days or every other day for 30 days. Behavioral testing occurred daily during the chlorpyrifos-exposure period and throughout a 30 day washout period to assess recovery. Cholinesterase activity was assessed 24 hours after the last exposure and after a 31 day washout period.Results: All chlorpyrifos-treated animals exhibited deficits in percent correct, an increase in omissions and premature responses without signs of impaired motivation or overt toxicity. Deficits in 5C-SRTT accuracy were significant well into the 30-day washout period despite recovery of cholinesterase activity.Conclusion: These results indicate that repeated exposure to chlorpyrifos lead to protracted impairments of sustained attention and an increase in impulsive behaviors in rats that may not be directly related to impaired cholinesterase activity.