Chronic impairments in spatial learning and memory in rats previously exposed to chlorpyrfos or diisopropylfluorophosphate

Neurotoxicol Teratol. 2012 Jan-Feb;34(1):1-8. doi: 10.1016/j.ntt.2011.08.015. Epub 2011 Oct 17.

Abstract

The acute toxicity of organophosphates (OPs) has been studied extensively; however, much less attention has been given to the subject of repeated exposures that are not associated with overt signs of toxicity (i.e., subthreshold exposures). The objective of this study was to determine if the protracted spatial learning impairments we have observed previously after repeated subthreshold exposures to the insecticide chlorpyrifos (CPF) or the alkylphosphate OP, diisopropylfluorophosphate (DFP) persisted for longer periods after exposure. Male Wistar rats (beginning at two months of age) were initially injected subcutaneously with CPF (10.0 or 18.0mg/kg) or DFP (0.25 or 0.75 mg/kg) every other day for 30 days. After an extended OP-free washout period (behavioral testing begun 50 days after the last OP exposure), rats previously exposed to CPF, but not DFP, were impaired in a radial arm maze (RAM) win-shift task as well as a delayed non-match to position procedure. Later experiments (i.e., beginning 140 days after the last OP exposure) revealed impairments in the acquisition of a water maze hidden platform task associated with both OPs. However, only rats previously exposed to DFP were impaired in a second phase of testing when the platform location was changed (indicative of deficits of cognitive flexibility). These results indicate, therefore, that repeated, subthreshold exposures to CPF and DFP may lead to chronic deficits in spatial learning and memory (i.e., long after cholinesterase inhibition has abated) and that insecticide and alkylphosphate-based OPs may have differential effects depending on the cognitive domain evaluated.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chlorpyrifos / toxicity*
  • Cholinesterase Inhibitors / toxicity*
  • Chronic Disease
  • Disease Models, Animal
  • Isoflurophate / toxicity*
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / diagnosis
  • Learning Disabilities / physiopathology
  • Male
  • Memory Disorders / chemically induced*
  • Memory Disorders / diagnosis
  • Memory Disorders / physiopathology
  • Rats
  • Rats, Wistar

Substances

  • Cholinesterase Inhibitors
  • Isoflurophate
  • Chlorpyrifos