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Research ArticleNEUROPHARMACOLOGY

Repeated Exposures to Subthreshold Doses of Chlorpyrifos in Rats: Hippocampal Damage, Impaired Axonal Transport, and Deficits in Spatial Learning

A. V. Terry Jr., J. D. Stone, J. J. Buccafusco, D. W. Sickles, A. Sood and M. A. Prendergast
Journal of Pharmacology and Experimental Therapeutics April 2003, 305 (1) 375-384; DOI: https://doi.org/10.1124/jpet.102.041897
A. V. Terry Jr.
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J. D. Stone
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J. J. Buccafusco
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D. W. Sickles
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A. Sood
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M. A. Prendergast
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Abstract

Organophosphorus (OP) compounds are detectable in the environment for years after use and endanger many populations. Although the effects of acutely toxic doses of many OP compounds are well described, much less is known about repeated low-level exposures. The purpose of these studies was to further evaluate potential toxicological effects of the extensively used OP pesticide chlorpyrifos (CPF) in rats. CPF, across a range of subthreshold doses (i.e., for acute toxicity), reduced rearing and sniffing activity and the magnitude of weight gain over 14 days of repeated exposure. Performance in a spatial learning task was impaired after 14 days of exposure to CPF (18.0 and 25.0 mg/kg) when testing was initiated 24 h after the last injection but not after a 14-day washout. However, inhibition of both fast anterograde and retrograde axonal transport was observed for up to 20 days after exposure to 25.0 mg/kg CPF. Studies using hippocampal cultures indicated that 8 days of continuous exposure to the parent compound, CPF (≥100 μM), resulted in cell toxicity and death. Furthermore, a dose (2.5 mg/kg) of CPF that had no effects on weight gain or memory performance when administered 5 days per week over 38 days impaired forelimb grip strength in the later days of testing. Collectively, these results indicate that repeated exposures to subthreshold doses of CPF may lead to growth retardation, behavioral abnormalities, and muscle weakness. Some of these symptoms may be attributed to effects of the OP on axonal transport.

Footnotes

  • DOI: 10.1124/jpet.102.041897

  • Abbreviations:
    OP
    organophosphate
    CPF
    chlorpyrifos
    AChE
    acetylcholinesterase
    OPIDN
    organophosphorus-induced delayed neuropathies
    AXT
    axonal transport
    DIC
    differential interference contrast
    DFP
    diisopropyl fluorophosphate
    PI
    propidium iodide
    ANOVA
    analysis of variance
    • Received July 18, 2002.
    • Accepted December 11, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 305 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 305, Issue 1
1 Apr 2003
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Research ArticleNEUROPHARMACOLOGY

Repeated Exposures to Subthreshold Doses of Chlorpyrifos in Rats: Hippocampal Damage, Impaired Axonal Transport, and Deficits in Spatial Learning

A. V. Terry, J. D. Stone, J. J. Buccafusco, D. W. Sickles, A. Sood and M. A. Prendergast
Journal of Pharmacology and Experimental Therapeutics April 1, 2003, 305 (1) 375-384; DOI: https://doi.org/10.1124/jpet.102.041897

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Research ArticleNEUROPHARMACOLOGY

Repeated Exposures to Subthreshold Doses of Chlorpyrifos in Rats: Hippocampal Damage, Impaired Axonal Transport, and Deficits in Spatial Learning

A. V. Terry, J. D. Stone, J. J. Buccafusco, D. W. Sickles, A. Sood and M. A. Prendergast
Journal of Pharmacology and Experimental Therapeutics April 1, 2003, 305 (1) 375-384; DOI: https://doi.org/10.1124/jpet.102.041897
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