title: Repeated exposures to low-level chlorpyrifos results in impairments in sustained attention and increased impulsivity in rats.
abstract: Organophosphates such as chlorpyrifos (CPF) are among the most commonly used pesticides in the world. Therefore, it is not surprising that measurable levels of organophosphates (including CPF) are found in over 50% of fresh fruits, vegetables and grains that we consume and that approximately 80% of adults in the US have detectable levels of CPF metabolites in their urine. It is well known that acute exposure to organophosphates can cause cognitive deficits; however, the effects of daily or intermittent contact with low levels of organophosphates (often reflective of environmental exposures) are not well understood. The objective of this study was to determine if repeated low-level exposures to CPF impaired the performance of the 5-Choice Serial Reaction Time Task (5C-SRTT), an animal model of sustained attention. Adult rats were trained to stably perform the 5C-SRTT, then treated with vehicle or CPF 18.0 mg/kg daily for 14 consecutive days or every other day for 30 days. Behavioral testing occurred daily during the CPF-exposure period and throughout a 30 day washout period to assess recovery. All CPF-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 apparent well into the 30 day washout period despite significant recovery of cholinesterase activity. These results indicate that repeated exposures to relatively low levels of chlorpyrifos lead to protracted impairments of sustained attention and an increase in impulsive behaviors in rats.
authors.affiliation: Program of Clinical and Experimental Therapeutics, University of Georgia, College of Pharmacy, Augusta, GA, 30912, United States.
authors.forename: M L
authors.initials: ML
authors.lastname: Middlemore-Risher
authors.forename: J J
authors.initials: JJ
authors.lastname: Buccafusco
authors.forename: A V
authors.initials: AV
authors.lastname: Terry
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000139:chemically induced*; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D002802:Cholinesterases; D004390:Chlorpyrifos