Effects of Chronic Dietary and Repeated Acute Exposure to Chlorpyrifos on Learning and Sustained Attention in Rats

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Abstract
Cognitive and motor impairment often follow acute poisoning with an organophosphorous (OP) pesticide. However, the persistence of these effects and the conditions necessary for their appearance are not clear: two specific concerns are whether symptomatic poisoning is necessary for persistent effects, and whether inhibition of cholinesterase (ChE) activity is a protective metric of OP exposure. This study examined the effects of chronic dietary and repeated high-level acute exposure to the pesticide chlorpyrifos (diethyl 3,5,6-trichloro-2-pyridyl phosphorothionate, CPF) on learning and attention. Beginning at 3 months of age, male Long-Evans rats received dietary CPF at a daily dose of 0, 1, or 5 mg/kg for 1 year. Half of each dietary group also received an acute oral dose of CPF (initial dose at 60 mg/kg, 5 doses at 45 mg/kg) every 2 months. Beginning 2 weeks before the fourth acute dose, behavioral assessments were conducted on the eight rats in each of the six exposure groups (0-Oil, 0-CPF, 1-Oil, 1-CPF, 5-Oil, and 5-CPF). Using an auto-shaping procedure, the groups learned to press a lever for food in the following order: 5-Oil, 5-CPF, 1-Oil, and 0-Oil. The 0-CPF and 1-CPF groups did not learn the response in three 50-trial sessions. Chronic CPF did not affect acquisition of other behaviors required by a signal detection task (SDT) designed to assess sustained attention. The sixth acute CPF dose significantly disrupted the SDT in all dosed groups. Two months after the end of dosing, performance of the SDT was impaired in the 5-CPF group. These data suggest that learning the contingency between an action and reward may be accelerated by chronic exposure to CPF and inhibited by previous symptomatic exposure to CPF, and that persistent cognitive impairment may follow if CPF exposure inhibits brain ChE activity and is accompanied by acute doses sufficient to induce signs of toxicity.