Skip to main content
SpringerLink
Log in

Physiological Compensation for Toxic Actions of Organophosphate Insecticides

  • Chapter
Insecticide Action

  • 105 Accesses

Abstract

The neurochemical changes which could serve as physiological compensatory mechanisms during recovery from a high level acute intoxication with an organophosphate anticholinesterase were studied concurrently with behavioral deficits resulting from the intoxication. Paraoxon, the active metabolite of the common insecticide parathion, was administered to male rats at lethal (antidoted with atropine) and high sub-lethal levels. Brain acetylcholinesterase, the target enzyme, was inhibited about 90% on the day of treatment, and recovered slowly over the next several days. Rats displayed some relatively small and transient behavioral deficits 1 and 2 days after treatment with paraoxon in an active avoidance protocol. Of four neurochemical parameters in the brain which could have helped compensate for the cholinergic hyperactivity induced by the acetylcholinesterase inhibition (high affinity choline uptake, choline acetyltransferase, acetylcholine release and muscarinic acetylcholine receptors), none showed definitive changes at the time points monitored. Thus, unlike the response to chronic exposures to organophosphate anticholineterases, an acute intoxication, even at high dose levels, does not seem to result in the employment of cholinergic compensatory mechanisms despite persistent acetylcholinesterase inhibition.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aas, P., Veiteberg, T. A., and Fonnum, F., 1987, Acute and sub-acute inhalation of an organophosphate induce alteration of cholinergic muscarinic receptors, Biochem. Pharmacol., 36: 1261.

    Article  PubMed  CAS  Google Scholar 

  • Atweh, S., Simon, J. R., and Kuhar, M. J., 1975, Utilization of sodium-dependent high affinity choline uptake in vitroas a measure of the activity of cholinergic neurons in vivo, Life Sci., 17: 1535.

    Article  PubMed  CAS  Google Scholar 

  • Barker, L. A., and Mittag, T. W., 1975, Comparative studies of substrates and inhibitors of choline transport and choline acetyltransferase. J. Pharmacol. Exptl. Therapeut., 192: 86.

    CAS  Google Scholar 

  • Beninger, R. J., Jhamandas, K., Boegman, R. J., and El-Defrawy, S. R., 1986a, Effects of scopolamine and unilateral lesions of the basal forebrain on T-maze spatial discrimination and alteration in rats, Pharmacol. Biochem. Behav., 24: 1353.

    Article  CAS  Google Scholar 

  • Beninger, R. J., Wirsching, B. A., Jhamandas, K., Boegman, R. J., and El-Defrawy, L.R., 1986b, Effects of altered cholinergic function on working and reference momory in the rat, Can. J. Physiol. Pharmacol., 64: 376.

    Article  CAS  Google Scholar 

  • Berends, F., Posthumus, C. H., Van der Sluys, I., and Deierkauf, F. A., 1959, The chemical basis of the “aging process” of DFP-inhibited pseudocholinesterase, Biochem. Biophys. Acta., 34: 576.

    Article  CAS  Google Scholar 

  • Bermudez-Rattoni, F., Mujica-Gozalez, M., and Prado-Alcala, R. A., 1986, Is cholinergic activity of the striatum involved in the acquisition of positively-motivated behavior? Pharmacol. Biochem. Behay., 24: 715.

    Article  CAS  Google Scholar 

  • Bignami, G., and Giardini, V., 1983, Cholinergic effects: critical treatment-behavior interactions in paraoxon tolerance, in: “Applications in Behavior, Pharmacology and Toxicology” (Lecture Workshop), G. Zbinden, V. Cuomo, and G. Racagni, ed., Raven Press, New York.

    Google Scholar 

  • Bignami, G., Rosic, N., Michalek, H., Milosevic, M., and Gatti, G. L., 1975, Behavioral toxicity of anticholinesterase agents: Methodological, neuvochemical and neuropsychological aspects, in: “Behavioral Toxicology”, B. Weiss and V.G. Laties, ed., Plenum Press, New York.

    Google Scholar 

  • Brezenoff, H. E., McGee, J., and Hymowitz, N., 1985, Effect of soman on schedule-controlled behavior and brain acetylcholinesterase in rats, Life Sci., 37: 2421.

    Article  PubMed  CAS  Google Scholar 

  • Brush, F. R., 1962, The effects of intertrial interval on avoidance learning in the rat, J. Comp. Physiol. Psychol., 55: 888.

    Article  PubMed  CAS  Google Scholar 

  • Chambers, J. E., Wiygul, S. M., Harkness, J. E., and Chambers, H. W., 1988, Effects of acute paraoxon and atropine exposures on retention of shuttle avoidance behavior in rats, Neurosci. Res. Comm., In press. Chambers, J. E., and Chambers, H. W., 1988, Effect of the anticholinesterase paraoxon on shuttle avoidance behavior and brain muscarinic receptors, Toxicologist, 8: 76.

    Google Scholar 

  • Chambers, H. W., and Chambers, J. E., 1989, An investigation of acetylcholinesterase inhibition and aging and choline acetyltransferase activity following a high level acute exposure to paraoxon, Pestic. Biochem. Physiol. 33: 125

    Article  CAS  Google Scholar 

  • Churchill, L., Pazdernik, T. L., Jackson, J. L., Nelson, S. R., Samson, F.E., and McDonough, J. H., 1984a, Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman, J. Neurosci., 4: 2069.

    PubMed  CAS  Google Scholar 

  • Churchill, L., Pazdernik, T. L. Samson, F., and Nelson, S. R., 1984b, Topographical distribution of down-regulated muscarinic receptors in rat brains after repeated exposure to diisopropylphosphonofluoridate, Neurosci., 11: 463.

    Article  CAS  Google Scholar 

  • Davis, W. M., and Hatoum, H. T., 1987, Comparison of stimulants and hallucinogens on shuttle avoidance in rats, Gen. Pharmacol., 18: 123.

    Google Scholar 

  • Desi, I., 1983, Neurotoxicological investigation of pesticides in animal experiments, Neurobeh. Toxicol. Teratol., 5: 503.

    Google Scholar 

  • Ellman, G. L., Courtney, K. D., Andres, V., and Featherstone, R. M., 1961, A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol., 7: 88.

    CAS  Google Scholar 

  • Fonnum, F., 1975, A rapid radiochemical method for the determination of choline acetyltransferase, J. Neurochem., 24: 407.

    Article  PubMed  CAS  Google Scholar 

  • Gaines, T. B., and Linder, R. E., 1986, Acute toxicity of pesticides in adult and weanling rats, Fundam. Appl. Toxicol., 7: 299.

    Article  CAS  Google Scholar 

  • Gardner, R., Ray, R., Frandkenheim, J., Wallace, K., Loss, M., and Robichaud, R., 1984, A possible mechanism for diisopropylfluorophosphate-induced memory loss in rats, Pharmacol. Biochem. Behay., 21: 43.

    Article  CAS  Google Scholar 

  • Gazit, H., Silman, I., and Dudai, Y., 1979, Administration of an organophosphate causes a decrease in muscarinic receptor level in rat brain, Brain Res., 174: 351.

    Article  PubMed  CAS  Google Scholar 

  • Geller, I., Hartmann, R. J., Leal, B. Z., Haines, R. J., and Gause, E. M., 1984, Effects of the irreversible acetylcholinesterase inhibitor soman on match-to-sample behavior of the juvenile baboon, Proc. West. Pharmacol. Soc., 27: 217.

    CAS  Google Scholar 

  • Gonzalez, L. P., and Ellinwood, Jr., E. H., 1984, Cholinergic modulation of stimulant-induced behavior, Pharmacol. Biochem. Behay., 20: 397.

    Article  CAS  Google Scholar 

  • Haga, T., 1971, Synthesis and release of [14C]acetylcholine in synaptosomes, J. Neurochem., 18: 781.

    Article  PubMed  CAS  Google Scholar 

  • Haggerty, G. C., Kurtz, P. J., and Armstrong, R. D., 1986, Duration and intensity of behavioral change after sublethal exposure to soman in rats, Neurobeh. Toxicol. Teratol., 8: 695.

    CAS  Google Scholar 

  • Hayes, W. J., Jr., 1969, Pesticides and human toxicity, Ann. New York Acad. Sci., 160: 40.

    Article  CAS  Google Scholar 

  • Kaita, A. A., and Goldberg, A. M., 1969, Control of acetylcholine synthesis-the inhibition of choline acetyltransferase by acetylcholine, J. Neurochem., 16: 1185.

    Article  PubMed  CAS  Google Scholar 

  • Kuhar, M. J., and Murrin, L. C., 1978, Sodium-dependent, high affinity choline uptake, J. Neurochem., 30: 15.

    Article  PubMed  CAS  Google Scholar 

  • Lehotzky, K., 1982, Effect of pesticides on central and peripheral nervous system function in rats, Neurobeh. Toxicol. Teratol., 4: 665.

    CAS  Google Scholar 

  • Lerer, B., Altman, H., and Stanley, M., 1984, Enhancement of memory by a cholinesterase inhibitor associated with muscarinic receptor down-regulation, Pharmacol. Biochem. Behay., 21: 467.

    Article  CAS  Google Scholar 

  • Lim, D. K., Hoskins, B., and Ho, I. K., 1986, Correlation of muscarinic receptor density and acetylcholinesterase in repeated DFP-treated rats after termination of DFP administration, European J. Pharmacol., 123: 223.

    CAS  Google Scholar 

  • McMillan, D. E., 1982, Effects of chronic administration of pesticides on schedule-controlled responding by rats and pigeons, in: “Effects of Chronic Exposures to Pesticides on Animal Systems”, J.E. Chambers and J.D. Yarbrough, ed., Raven Press, New York.

    Google Scholar 

  • Nemeth, E. F., and Cooper, J. R., 1979, Effects of somatostatin on acetylcholine release from rat hippocampal synaptosomes, Brain Res., 165: 166.

    Article  PubMed  CAS  Google Scholar 

  • Raffaele, K., Hughey, D., Wenk, G., Olton, D., Modrow, H., and McDonough, J., 1987, Long-term behavioral changes in rats following organophosphate exposure, Pharmacol. Biochem. Behay., 27: 407.

    Article  CAS  Google Scholar 

  • Rauch, S. L., and Raskin, L. A., 1984, Cholinergic mediation of spatial memory in the preweanling rat: application of the radial arm maze paradigm, Behay. Neurosci., 98: 35.

    CAS  Google Scholar 

  • Sanberg, P. R., Lehmann, J., and Fibiger, H. C., 1978, Impaired learning and memory after kainic acid lesions of the striatum: a behavioral model of Huntington’s disease, Brain Res., 149: 546.

    Article  PubMed  CAS  Google Scholar 

  • Sandberg, K., Sanberg, P., Hanin, I., Fisher, A., and Coyle, J. T., 1984, Cholinergic lesion of the striatum impairs acquisition and retention of a passive avoidance response, Behay. Neurosci., 98: 162.

    CAS  Google Scholar 

  • Schiller, G. D., 1979, Reduced binding of (3H)-quinuclidinyl benzilate associated with chronically low acetylcholinesterase activity, Life Sci., 24: 1159.

    Article  PubMed  CAS  Google Scholar 

  • Simon, J. R., Atweh, S., and Kuhar, M. J., 1976, Sodium-dependent high affinity choline uptake: a regulatory step in the synthesis of acetylcholine, J. Neurochem., 26: 909.

    Article  PubMed  CAS  Google Scholar 

  • Sivam, S. P., Norris, J. C., Lim, D. K., Hoskins, B., and Ho, I. K., 1983, The effect of acute and chronic cholinesterase inhibition with diisopropylfluorophosphate on muscarinic dopamine and GABA receptors of the rat striatum, J. Neurochem., 40: 1414.

    Article  PubMed  CAS  Google Scholar 

  • Smolen, T. N., Smolen, A., and Collins, A. C., 1986, Dissociation of decreased numbers of muscarinic receptors from tolerance to DFP, Pharmacol. Biochem. Behay., 25: 1293.

    Article  CAS  Google Scholar 

  • Uchida, S., Takeyasu, K., Matsuda, T., and Yoshida, H., 1979, Changes in muscarinic acetylcholine receptors of mice by chronic administrations of diisopropylfluorophosphate and papaverine, Life Sci., 24: 1805.

    Article  PubMed  CAS  Google Scholar 

  • Upchurch, M., and Wehner, J. M., 1987, Effects of chronic diisopropylfluorophosphate treatment on spatial learning in mice, Pharmacol. Biochem. Behay., 27: 143.

    Article  CAS  Google Scholar 

  • Walsh, T. J., Tilson, H. A., DeHaven, D. L., Mailman, R. B., Fisher, A., and Hanin, I., 1984, AF64A, a cholinergie neurotoxin, selectively depletes acetylcholine in hippocampus and cortex, and produces long-term passive avoidance and radial-arm maze deficits in rats, Brain Res., 321: 91.

    Article  PubMed  CAS  Google Scholar 

  • Wecker, L., Mobley, P. L., and Dettbarn, W.-D., 1977, Central cholinergie mechanisms underlying adaptation to reduce cholinesterase activity, Biochem. Pharmacol., 26: 633.

    CAS  Google Scholar 

  • Wenk, G., Hughey, D., Boundy, V., Kim, A., Walker, L., and Olton, D., 1987, Neurotransmitters and memory: role of cholinergie, serotinergic and noradrenergic systems, Behay. Neurosci., 101: 325.

    Google Scholar 

  • Woolley, D. E., Chernobieff, J. R., and Reiter, L. W., 1979, Effects of parathion on the mammalian nervous system, in: “Neurotoxicity of Insecticides and Pheromones”, T. Narahashi, ed., Plenum Press, New York

    Google Scholar 

  • Yamada, S., Isogai, M., Okudaira, H., and Hayashi, E., 1983, Correlation between cholinesterase inhibition and reduction in muscarinic receptors and choline uptake by repeated diisopropylfluorophosphate administration: antagonism by physostigmine and atropine, J. Pharmacol. Exptl. Therapeut., 226: 519.

    CAS  Google Scholar 

  • Yamamura, H. I., and Snyder, S. H., 1973, High affinity transport of choline into synaptosomes of rat brain, J. Neurochem., 21: 1355.

    Article  PubMed  CAS  Google Scholar 

  • Yamamura, H. I., and Snyder, S. H., 1974, Muscarinic cholinergic binding in rat brain, Proc. Nat. Acad. Sci., 71: 1725.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Biological Sciences and Entomology, Mississippi State University, Mississippi State, Mississippi, 39762, USA

    Janice E. Chambers & Howard W. Chambers

Authors
  1. Janice E. Chambers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Howard W. Chambers
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Northwestern University Medical School, Chicago, Illinois, USA

    Toshio Narahashi

  2. Mississippi State University, Mississippi State, Mississippi, USA

    Janice E. Chambers

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Plenum Press, New York

About this chapter

Cite this chapter

Chambers, J.E., Chambers, H.W. (1989). Physiological Compensation for Toxic Actions of Organophosphate Insecticides. In: Narahashi, T., Chambers, J.E. (eds) Insecticide Action. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1324-3_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-1324-3_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-1326-7

  • Online ISBN: 978-1-4684-1324-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation