Long-term neurochemical and behavioral effects induced by acute chlorpyrifos treatment

Abstract

A single dose of the organophosphate insecticide O, O′-diethyl- O-3,5,6-trichloro-2-pyridylphosphorothioate [chlorpyrifos (CPF), 279 mg/kg, SC] caused extensive inhibition of cortical and striatal cholinesterase (ChE) activity in adult rats at 2 (94–96%), 4 (83–84%), and 6(58–60%) weeks after treatment. These persistent changes in ChE activity were concomitant with reductions in muscarinic receptor binding sites in cortex (34, 33, and 18% reduction in B max) and striatum (48, 40, and 23% reduction in B max) at 2, 4, and 6 weeks after exposure. Neither ChE activities nor muscarinic receptor densities were different from control levels at 12 weeks after exposure. CPF treatment caused a reduction in locomotor activity for the first 2 days after treatment, after which basal activity levels were not different from controls. CPF-treated rats showed higher activity relative to controls, however, following challenge with scopolamine (1 mg/kg, IP) at 2, 4, 6, 8, and 12 weeks after treatment. These data indicate that acute exposure to CPF in adult rats can cause long-term neurobehavioral changes that may persist following the recovery of neurochemical parameters associated with exposure and tolerance to cholinesterase hibitors.