Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Motor functions but not learning and memory are impaired upon repeated exposure to sub-lethal doses of methyl parathion

Summary

Our previous work showed that repeated exposure to methyl parathion (MP) caused a prolonged inhibition of acetylcholinesterase (AChE) activity (∼80%) and down-regulation of M1 and M2 muscarinic receptors (up to 38%) in rats at brain regions, including frontal cortex, striatum, hippocampus and thalamus. In the present neurobehavioral study, we found this repeated MP treatment had suppressant effects on rat’s locomotor activity. However, we observed no evidence of long-term effects of MP on associative learning and memory. Our data demonstrated that repeated exposure to MP caused some functional deficits in CNS, but motor activity and associative learning/memory process might differ in the sensitivity to its toxic effect. The motor dysfunctions in MP-treated rats may be mediated via reciprocal balance between cholinergic and dopaminergic systems at striatum following cholinergic over-stimulation. Our findings also suggest that the CNS deficits induced by repeated exposure to MP or other organophosphate (OP) pesticides cannot be attributed entirely to the inhibition of AChE. To accurately assess the neuro-toxic risk by occupational exposure to sub-lethal doses of MP, novel biomarkers besides in vivo anticholinesterase potency are needed.

References

  1. 1.

    Karczmar A.G. (1984) Acute and long lasting central actions of organophosphorus agents. Fundam. Appl. Toxicol. 4: S1–S17

  2. 2.

    Hoskins B. and Ho I.K. (1992) Tolerance to organophosphorus cholinesterase insecticides. In: Chambers J.E., Levis P.E. (eds), Organophosphates: Chemistry, Fate, and Effects. Academic Press, San Diego, pp. 285–297

  3. 3.

    Russell R.W., Overstreet D.H. (1987) Mechanisms underlying sensitivity to organophosphorus anticholinesterase compounds. Prog. Neurobiol. 28: 97–129

  4. 4.

    Gershon S., Shaw F.H. (1961) Psychiatric sequelae of chronic exposure to organophosphorus insecticides. Lancet 11: 1371–1374

  5. 5.

    Metcalf D.R., Holmes J.H. (1969) EEG, psychological and neurological alterations in humans with organophosphorus exposure. Ann. N.Y. Acad. Sci. 160: 357–365

  6. 6.

    Le Couteur D.G., McLean A.J., Taylor M.C., Woodham B.L., Board P.G. (1999) Pesticides and Parkinson’s disease. Biomed. Pharmacother. 53: 122–130

  7. 7.

    Carriero D.L., Outslay G., Mayorga A.J., Aberman J., Gianutsos G., Salamone J.D. (1997) Motor dysfunction produced by tacrine administration in rats. Pharmacol. Biochem. Behav. 58: 851–858

  8. 8.

    Ott B.R., Lannon M.C. (1992) Exacerbation of Parkinsonism by tacrine. Clin. Neuropharmacol. 15: 322–325

  9. 9.

    United States Environmental Protections Agency. Illegal indoor use of methyl parathion. Retrieved from http://www.epa.gov/pesticides/citizens/methyl.htm, 2000

  10. 10.

    Agency for Toxic Substances and Disease Registry. Illegal use of methyl parathion insecticide. Retrieved from http://www.atsdr.cdc.gov/alerts/961213.htm, 1996

  11. 11.

    Kramer R.E., Wellman S.E., Rockhold R.W., Baker R.C. (2002) Pharmacokinetics methyl parathion: a comparison following single intravenous, oral or dermal administration. J. Biomed. Sci. 9: 311–320

  12. 12.

    Sun T.T., Ma T.G., Ho I.K. (2003) Differential modulation of muscarinic receptors in the rat brain by repeated exposure to methyl parathion. J. Toxicol. Sci. 28: 427–438

  13. 13.

    Russell R.W., Booth R.A., Smith C.A., Jenden D.J., Roch M., Rice K.M., Lauretz S.D. (1989) Roles of neurotransmitter receptors in behavior: recovery of function following decreases in muscarinic receptor density induced by cholinesterase inhibition. Behav. Neurosci. 103: 881–892

  14. 14.

    Bushnell P.J., Padilla S.S., Ward T., Pope C.N., Olszyk V.B. (1991) Behavioral and neurochemical changes in rats dosed repeatedly with diisopropylfluorophosphate. J. Pharmacol. Exp. Ther. 256: 741–750

  15. 15.

    Gongora-Alfaro J.L., Hernandez-Lopez S., Martinez-Fong D., Flores G., Aceves J. (1996) Circling behavior elicited by cholinergic transmission in the substantia nigra pars compacta: involvement of nicotinic and muscarinic receptors. Neuroscience 71: 729–734

  16. 16.

    Cousins M.S., Sokolowski J.D., Salamone J.D. (1993) Different effects of nucleus accumbens and ventrolateral striatal dopamine depletions on instrumental response selection in the rat. Pharmacol. Biochem. Behav. 46: 943–951

  17. 17.

    Sivam S.P., Norris J.C., Lim D.K., Hoskins B., Ho I.K. (1983) Effects of acute and chronic cholinesterase inhibitor with diisopropylfluorophosphate on muscarinic, dopamine and GABA receptors of the rat striatum. J. Neurochem. 40: 1414–1422

  18. 18.

    Fernando J.C., Hoskins B., Ho I.K. (1984) Effect on striatal dopamine metabolism and differential motor behavior tolerance following chronic cholinesterase inhibition with diisopropylfluorophosphate. Pharmacol. Biochem. Behav. 20: 951–957

  19. 19.

    Costa L.G., Murphy S.D. (1982) Passive avoidance retention in mice tolerant to the organophosphorus insecticide disulfoton. Toxicol. Appl. Pharmacol. 65: 451- 458

  20. 20.

    Llorens J., Crofton K.M., Tilson H.A., Ali S.F., Mundy W.R. (1993) Characterization of disulfoton-induced behavioral and neurochemical effects following repeated exposure. Fundam. Appl. Toxicol. 20: 163–169

  21. 21.

    Gardner R., Ray R., Frankenheim J., Wallace K., Loss M., Robichaud R. (1984) A possible mechanism for diisopropylflurophosphate-induced memory loss in rats. Pharmacol. Biochem. Behav. 21: 43–46

  22. 22.

    Upchurch M., Wehner J.M. (1987) Effects of chronic diisopropylfluorophosphate treatment on spatial learning in mice. Pharmacol. Biochem. Behav. 27: 143–151

  23. 23.

    Bushnell P.J., Kelly K.L., Ward T.R. (1994) Repeated inhibition of cholinesterase by chlorpyrifos in rats: behavioral, neurochemical and pharmacological indices of tolerance. J. Pharmacol. Exp. Ther. 270: 15–25

  24. 24.

    Bushnell P.J., Pope C.N., Padilla S. (1993) Behavioral and neurochemical effects of acute chlorpyrifos in rats: tolerance to prolonged inhibition of cholinesterase. J. Pharmacol. Exp. Ther. 266: 1007–17

  25. 25.

    Jett D.A., Navoa R.V., Beckles R.A., McLemore G.L. (2001) Cognitive function and cholinergic neurochemistry in weanling rats exposed to chlorpyrifos. Toxicol. Appl. Pharmacol. 174: 89–98

  26. 26.

    Gupta R.C., Patterson G.T., Dettbarn W.D. (1986) Mechanisms of toxicity and tolerance to diisopropylphosphorofluoridate at the neuromuscular junction of the rat. Toxicol. Appl. Pharmacol. 84: 541–550

  27. 27.

    Klein W.L., Sullivan J., Skorupa A., Aguilar J.S. (1989) Plasticity of neuronal receptors. Fed. Am. Soc. Exp. Bio. J. 3: 2132–2140

  28. 28.

    Pope C.N. (1999) Organophosphorus pesticides: do they all have the same mechanism of toxicity? J. Toxicol. Environ. Health B Crit. Rev. 2: 161–181

Download references

Author information

Correspondence to Ing K. Ho.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sun, T., Paul, I.A. & Ho, I.K. Motor functions but not learning and memory are impaired upon repeated exposure to sub-lethal doses of methyl parathion. J Biomed Sci 13, 515–523 (2006). https://doi.org/10.1007/s11373-006-9075-9

Download citation

Keywords

  • learning and memory
  • methyl parathion
  • motor functions
  • repeated treatment