Skip to main content
SpringerLink
Log in

Methyl parathion increases neuronal activities in the rat locus coeruleus

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Exposure to organophosphate insecticides induces undesirable behavioral changes in humans, including anxiety and irritability, depression, cognitive disturbances and sleep disorders. Little information currently exists concerning the neural mechanisms underlying such behavioral changes. The brain stem locus coeruleus (LC) could be a mediator of organophosphate insecticide-induced behavioral toxicities since it contains high levels of acetylcholinesterase and is involved in the regulation of the sleep-wake cycle, attention, arousal, memory, and pathological processes, including anxiety and depression. In the present study, using a multi-wire recording technique, we examined the effects of methyl parathion, a commonly used organophosphate insecticide, on the firing patterns of LC neurons in rats. Systemic administration of a single dose of methyl parathion (1 mg/kg, i.v.) increased the spontaneous firing rates of LC neurons by 240% but did not change the temporal relationships among the activities of multiple LC neurons. This dose of methyl parathion induced a 50% decrease in blood acetylcholinesterase activity and a 48% decrease in LC acetylcholinesterase activity. The methyl parathion-induced excitation of LC neurons was reversed by administration of atropine sulfate, a muscarinic receptor antagonist, indicating an involvement of muscarinic receptors. The methyl parathion-induced increase in LC neuronal activity returned to normal within 30 min while the blood acetylcholinesterase activity remained inhibited for over 1 h. These data indicate that methyl parathion treatment can elicit excitation of LC neurons. Such excitation could contribute to the neuronal basis of organophosphate insecticide-induced behavioral changes in human.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aghajanian GK. Tolerance of locus coeruleus neurons to morphine and suppression of withdrawal response by clonidine. Nature 276:186–188;1978.

    Article  PubMed  Google Scholar 

  2. Albanese A, Butcher LL. Acetylcholinesterase and catecholamine distribution in the locus coeruleus of the rat. Brain Res Bull 5:127–134;1980.

    Article  PubMed  Google Scholar 

  3. Armstrong DM, Saper CB, Levey AI, Wainer BH, Terry RD. Distribution of cholinergic neurons in rat brain: Demonstrated by the immunocytochemical localization of choline acetyltransferase. J Comp Neurol 216:53–68;1983.

    Article  PubMed  Google Scholar 

  4. Anonymous: Methyl parathion comes inside. Environ Health Perspect 105:690–691;1997.

  5. Aston-Jones G, Bloom FE. Activation of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci 1:876–886;1981.

    PubMed  Google Scholar 

  6. Bird SJ, Kuhar MJ. Iontophoretic application of opiates to the locus coeruleus. Brain Res 122:523–533;1977.

    Article  PubMed  Google Scholar 

  7. Bowers MB, Goodman E, Sim VM. Some behavioral changes in man following anticholin-esterase administration. J Nerv Ment Dis 138:383–389;1964.

    PubMed  Google Scholar 

  8. Contrera JG, Mcleskey SW, Holopainen I, Xu J, Wojcik WJ. Muscarinic m2 receptors in cerebellar granule cell cultures from rat: Mechanism of short-term desensitization. J Pharmacol Exp Ther 265:433–440;1993.

    PubMed  Google Scholar 

  9. Corrodi H, Fuxe K, Hammer W, Sjoqvist F, Ungerstedt U. Oxotremorine and central monoamine neurons. Life Sci 6:2557–2566;1967.

    Article  PubMed  Google Scholar 

  10. D'Mello GD. Behavioral toxicity of anticholin-esterases in humans and animals — A review. Human Exp Toxicol 12:3–7;1993.

    Google Scholar 

  11. Geneser-Jensen FA, Blackstad TW. Distribution of acetylcholinesterase in the hippocampal region of the guinea pig. 1. Entorhinal area, parasubiculum, and presubiculum. Z Zell-forsch Mikrosk Anat 114:460–481;1971.

    Article  Google Scholar 

  12. Gershon S, Shaw FH. Psychiatric sequelae of chronic exposure to organophosphorus insecticides. Lancet i:1371–1374;1961.

    Article  Google Scholar 

  13. Guyenet PG, Aghajanian GK. ACh, substance P and met-enkephalin in the locus coeruleus: Pharmacological evidence for independent sites of action. Eur J Pharmacol 53:319–328;1979.

    Article  PubMed  Google Scholar 

  14. Egan TM, North RA. Acetylcholine acts on m2-muscarinic receptors to excite rat locus coeruleus neurones. Br J Pharmacol 85:733–735;1985.

    PubMed  Google Scholar 

  15. El-Etri MM, Nickell WT, Ennis M, Skau KA, Shipley MT. Brain norepinephrine reductions in soman-intoxicated rats: Association with convulsions and AChE inhibition, time course, and relation to other monoamines. Exp Neurol 118:153–163;1992.

    Article  PubMed  Google Scholar 

  16. Ellman GC, Courtney KO, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95;1961.

    Article  PubMed  Google Scholar 

  17. Engberg G, Svensson TH. Characterization of a cholinergic receptor on brain noradrenergic neurons: A microiontophoretic study. Neurosci Lett Suppl 3:361;1979.

    Google Scholar 

  18. Engberg G, Svensson TH. Pharmacoogical analysis of a cholinergic receptor mediated regulation of brain norepinephrine neurons. J Neural Transm 49:137–150;1980

    Article  PubMed  Google Scholar 

  19. Ennis M, Shipley MT. Tonic activation of locus coeruleus neurons by systemic or intracoerulear microinjection of an irreversible acetylcholinesterase inhibitor: Increased discharge rate and induction of C-fos. Exp Neurol 118:164–177;1992.

    Article  PubMed  Google Scholar 

  20. Environmental Protection Agency: Illegal Indoor Use of Methyl Parathion. Washington, EPA, 2002.

    Google Scholar 

  21. Foote SL, Bloom FE, Aston-Jones G. Nucleus locus coeruleus: New evidence of anatomical and physiological specificity. Physiol Rev 63:844–914;1983.

    PubMed  Google Scholar 

  22. Harro J, Oreland L. Depression as a spreading adjustment disorder of monoaminergic neurons: A case for primary implication of the locus coeruleus. Brain Res Rev 38:79–128;2001.

    Article  PubMed  Google Scholar 

  23. Kazic T. Norepinephrine synthesis and turnover in brain: Acceleration by physostigmine. In: Frontiers in Catecholamine Research (Usdin E, Snyder S. eds), pp 897–899. New York, Pergamon Press, 1973.

    Google Scholar 

  24. Kobayashi RM, Palkovits M, Hruska RE, Rothschild R, Yamamura HI. Regional distribution of muscarinic cholinergic receptors in rat brain. Brain Res 154:13–23;1978.

    Article  PubMed  Google Scholar 

  25. König P. A method for the quantification of synchrony and oscillatory properties of neuronal activity. J Neurosci Meth 54:31–37;1994.

    Article  Google Scholar 

  26. Korf J, Bunney BS, Aghajanian GK. Noradrenergic neurons: Morphine inhibition of spontaneous activity. Eur J Pharmacol 25:165–169;1974.

    Article  PubMed  Google Scholar 

  27. Kwatra MM, Leung E, Maan AC, McMahon KK, Ptasienski J, Green RD, Hosey MM. Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J Biol Chem 262:16314–16321;1987.

    PubMed  Google Scholar 

  28. Levin HS, Rodnitzky RL. Behavioral effects of organophosphate pesticides in man. Clin Toxicol 9:391–405;1976.

    PubMed  Google Scholar 

  29. Levin HS, Rodnitzky RL, Mick DL. Anxiety associated with exposure to organophosphate compounds. Arch Gen Psychiatry 33:225–228;1976.

    PubMed  Google Scholar 

  30. Lewis PR, Schon FEG. The localization of acetylcholinesterase in the locus coeruleus of the normal rat after 6-hydroxydopamine treatment. J Anat 120:373–385;1975.

    PubMed  Google Scholar 

  31. Lim DK, Porter AB, Hoskin B, Ho IK. Changes in ACh levels in the rat brain during subacute administration of diisopropylfluorosphate. Toxicol Appl Pharmacol 90:477–489;1987.

    Article  PubMed  Google Scholar 

  32. Longone P, Mocchetti I, Riva MA, Wojcik WJ. Characterization of a decrease in muscarinic m2 mRNA in cerebellar granule cells by carbachol. J Pharmacol Exp Ther 265:441–446;1993.

    PubMed  Google Scholar 

  33. Ma T, Cai Z, Wellman SE, Ho IK. A quantitative histochemistry technique for measuring regional distribution of acetylcholinesterase in the brain using digital scanning densitometry. Anal Biochem 296:18–28;2001.

    Article  PubMed  Google Scholar 

  34. Mason ST, Fibiger HC. Interaction between noradrenergic and cholinergic systems in the rat brain: Behavioral function in locomotor activity. Neuroscience 4:517–525;1979.

    Article  PubMed  Google Scholar 

  35. Masserano JM, King C. Effects on sleep of acetylcholine perfusion of the locus coeruleus of cats. Neuropharmacology 21:1163–1167;1982.

    Article  PubMed  Google Scholar 

  36. Namba T, Nolte CT, Jackrel J, Grob D. Poisoning due to organophosphate insecticides. Am J Med 50:475–492;1971.

    Article  PubMed  Google Scholar 

  37. Nostrandt AC, Duncan JA, Padilla S. A modified spectrophotometric method appropriate for measuring cholinesterase activity in tissue from carbaryl-treated animals. Fundam Appl Toxicol 21:196–203;1993.

    Article  PubMed  Google Scholar 

  38. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates, ed 2. Orlando, Academic Press, 1986.

    Google Scholar 

  39. Rotter A, Birdsall NJ, Burgen AS, Field PM, Smolen A, Raisman G. Muscarinic receptors in the central nervous system of the rat. 4. A comparison of the effects of axotomy and deafferentation on the binding of [3H]propylbenzilylcholine mustard and associated synaptic changes in the hypoglossal and pontine nuclei. Brain Res 180:207–224;1979.

    PubMed  Google Scholar 

  40. Redmond DE. Studies of the nucleus locus coeruleus in monkeys and hypotheses for neuropsychopharmacology. In: Psychopharmacology: The Third Generation of Progress (Meltzer HY, ed.), pp 967–975. New York, Raven Press, 1987.

    Google Scholar 

  41. Satoh K, Fibiger HC. Cholinergic neurons of the laterodorsal tegmental nucleus: Efferent and afferent connections. J Comp Neurol 253:277–302;1986.

    Article  PubMed  Google Scholar 

  42. Singewald N, Sharp T. Neuroanatomical targets of anxiogenic drugs in the hindbrain as revealed by Fos immunocytochemistry. Neuroscience 98:759–770;2000.

    Article  PubMed  Google Scholar 

  43. Spiegel R. Effects of RS-86, an orally active cholinergic agonist on sleep in man. Psychiatry Res 11:1–13;1984.

    Article  PubMed  Google Scholar 

  44. Svensson TH, Engberg G. Effect of nicotine on single cell activity in the noradrenergic nucleus locus coeruleus. Acta Physiol Scand Suppl 479:31–34;1980.

    PubMed  Google Scholar 

  45. Usher M, Cohen JD, Servan-Schreiber D, Rajkowski J, Aston-Jones G. The role of locus coeruleus in the regulation of cognitive performance. Science 283:549–554;1999.

    Article  PubMed  Google Scholar 

  46. Valentino RJ, Wehby RG. Morphine effects on locus coeruleus neurons are dependent on the state of arousal and availability of external stimuli: Studies in anesthetized and unanesthetized rats. J Pharmacol Exp Ther 244:1178–1186;1988.

    PubMed  Google Scholar 

  47. van Kampen EJ, Zijlstra WG. Spectrophotometry of hemoglobin and hemoglobin derivatives. Adv Clin Chem 23:199–255;1983.

    PubMed  Google Scholar 

  48. Waynforth HB, Flecknell PA. Experimental and Surgical Techniques in the Rat, ed 2. New York, Academic Press, 2001.

    Google Scholar 

  49. Woolf NJ. Cholinergic systems in mammalian brain and spinal cord. Prog Neurobiol 37:475–524;1991.

    Article  PubMed  Google Scholar 

  50. Xu J, Chuang DM. Muscarinic acetylcholine receptor-mediated phosphoinositide turnover in cultured cerebellar granule cells: Desensitization by receptor agonists. J Pharmacol Exp Ther 242:238–244;1987.

    PubMed  Google Scholar 

  51. Zhu H, Rockhold RW, Baker RC, Kramer RE, Ho IK. Effects of repeated or single dermal administration of methyl parathion on behavior and cholinesterase activity in rats. J Biomed Sci 8:467–474;2001.

    Google Scholar 

  52. Zhu H, Zhou W. Morphine induces synchronous oscillatory discharges in the rat locus coeruleus. J Neurosci 21:RC179;2001

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Miss., USA

    Hong Zhu PhD, Tangen Ma, Ing K. Ho & Robin W. Rockhold

  2. Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, 39216, Jackson, MS, USA

    Hong Zhu PhD, Wu Zhou & Xiao R. Li

Authors
  1. Hong Zhu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wu Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao R. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tangen Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ing K. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robin W. Rockhold
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, H., Zhou, W., Li, X.R. et al. Methyl parathion increases neuronal activities in the rat locus coeruleus. J Biomed Sci 11, 732–738 (2004). https://doi.org/10.1007/BF02254357

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02254357

Key Words

Search

Navigation