Effects of chronic, low-level organophosphate exposure on delayed recall, discrimination, and spatial learning in monkeys and rats

Mark A. Prendergast, Alvin V. Terry, Jerry J. Buccafusco

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Chronic exposure to low levels of organophosphate (OP) compounds impairs acetylcholine (ACh) degradation by acetylcholinesterase (ACHE) and, in humans, may produce lasting neurotoxicity affecting cognitive function. The present studies examined the ability of such exposure to impair performance of well-learned cognitive tasks in two species, nonhuman primates and rats. During 25 days of exposure to a 0.01 mg/kg dose of the OP diisopropylfluorophosphate (DFP), mature adult monkeys were not impaired in their performance of a well-learned delayed matching-to-sample task (DMTS). However, erythrocyte AChE activity was reduced from predrug levels by 76.26 ± 3.33% by 14 days after the initiation of DFP administration. Following titration of DFP to a 0.015 mg/kg dose for 15 days, DMTS performance remained at or above baseline levels. DMTS accuracy was moderately, but not significantly, reduced after titration to a dose of 0.02 mg/kg. However, decrements were associated with mild, overt symptoms of OP toxicity and performance returned to baseline levels after withdrawal from OP exposure. In rats, chronic exposure to a low-dose regimen of DFP (0.25 mg/kg/day for 14 days) impaired the ability to initially learn a spatial navigation task, but did not impair performance of previously learned stimulus discrimination and spatial navigation tasks. These data indicate that performance of memory tasks dependent upon reference concepts is not impaired by OP exposure regimens that impair acquisition of novel cognitive tasks prior to the onset of overt toxicity.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalNeurotoxicology and Teratology
Volume20
Issue number2
DOIs
StatePublished - Mar 1 1998

Keywords

  • Acetylcholine
  • Cholinesterase
  • DFP
  • Inhibitor
  • Memory Monkey
  • Organophosphate

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Effects of chronic, low-level organophosphate exposure on delayed recall, discrimination, and spatial learning in monkeys and rats'. Together they form a unique fingerprint.

  • Cite this