Neurochemical Journal

, Volume 12, Issue 1, pp 48–52 | Cite as

Age Related Effects of Levodopa on Rat Brain Striatal Acetylcholinesterase

  • M. Messripour
  • M. M. Gheisary
  • A. Mesripour
Experimental Articles


Long-term treatment of Parkinson’s disease (PD) with levodopa is accompanied by dyskinesia. Alteration in striatal acetylcholine signaling is partly responsible, but the involved mechanisms have yet to be determined. This study aimed to compare repeated levodopa treatment on dopamine (DA) content and acetylcholinesterase (AChE) activity in the young and old rat brain striatum. Male Wistar rats (3 and 30 months old) were injected with a mixture of levodopa + carbidopa (10 + 1 mg/kg). Control animals received normal saline only. Rats were killed and brain striatum was homogenized and centrifuged at 4°C. AChE activity was assayed in the supernatant and DA was extracted from the homogenate and measured by high performance liquid chromatography with electrochemical detection. The levels of DA in young and aged rats were 53.1 ± 4.5 and 28.4 ± 3.1 nmol/ g wet weight tissue respectively. AChE activity in corresponding supernatant was 32.4 ± 2.7 and 58.1 ± 3.3 μmol/min/mg protein. A single dose of the drug mixture increased DA content and decreased AChE activity in both ages. When the drug mixture was injected daily for a period of 30 days, a lower DA content and a higher AChE activity were observed, though the changes were more pronounced in the aged animals. The result indicates that long-term treatment with levodopa + carbidopa in aged rat renders a dramatic rise in the striatal AChE, leading to imbalance ACh/DA levels in the striatum. It is concluded that AChE might be considered as a therapeutic target for combating levodopa-induced dyskinesia affecting PD patients.


aging acetylcholine dopamine dyskinesia Parkinson’s disease 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kalia, L.V. and Lang, A.E., Lancet, 2015, vol. 386, no. 9996, pp. 896–912.CrossRefPubMedGoogle Scholar
  2. 2.
    Roper, J.A., Kang, N., Ben, J., Cauraugh, J.H., Okun, M.S., and Hass, C.J., J. Neurol., 2016, vol. 263, no. 6, pp. 1195–1203.CrossRefPubMedGoogle Scholar
  3. 3.
    Suppa, A., Bologna, M., Conte, A., Berardelli, A., and Fabbrini, G., Exp. Rev. Neurotherap., 2017, vol. 17, no. 2, pp. 181–192.CrossRefGoogle Scholar
  4. 4.
    Tomlinson, C.T., Stowe, R., Patei, S., Rick, C., Gray, R., and Clarke, C.E., Mov. Disord., 2010, vol. 25, no. 15, pp. 2649–2653.CrossRefPubMedGoogle Scholar
  5. 5.
    Fabbrini, G., Brotchie, J.M., Grandas, F., Nomoto, M., and Goetz, C.G. Mov. Disord., 2007, vol. 22. no. 10, pp. 1379–1389.CrossRefPubMedGoogle Scholar
  6. 6.
    Dekundy, A., Lundblad, M., Danysz, W., and Cenci, M.A., Behav. Brain Res., 2007, vol. 179, no. 1, pp. 76–89.CrossRefPubMedGoogle Scholar
  7. 7.
    Conti, M.M., Meadows, S.M., Melikhov-Sosin, M., Lindenbach, D., Hallmark, J., Werner, D.F., and Bishop, C., Neuropharmacology, 2016, vol. 110 (part A), pp. 125–134.CrossRefPubMedGoogle Scholar
  8. 8.
    Pahwa, R. and Lyons, K.E., Cur. Med. Res. Opin., 2009, vol. 25, no. 4, pp. 841–849.CrossRefGoogle Scholar
  9. 9.
    Hernández, V.S., Luquín, S., Jáuregui-Huerta, F., Corona-Morales, A.A., Medina, M.P., Ruíz-Velasco, S., and Zhang, L., Neuropharmacology, 2014, vol. 82, pp. 88–100.CrossRefPubMedGoogle Scholar
  10. 10.
    Alcantara, A.A., Chen, V., Herring, B.E., Mendenhall, J.M., and Berlanga, M.L. Brain Res., 2003, vol. 986, nos. 1–2, pp. 22–29.CrossRefPubMedGoogle Scholar
  11. 11.
    Threlfell, S., Lalic, T., Platt, N.J., Jennings, K.A., Deisseroth, K., and Cragg, S.J. Neuron, 2012, vol. 75, no. 1, pp. 58–64.CrossRefPubMedGoogle Scholar
  12. 12.
    Chuhma, N., Mingote, S., Moore, H., and Rayport, S., Neuron, 2014, vol. 81, no. 4, pp. 901–912.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Straub, C., Tritsch, N.X., Hagan, N.A., Gu, C., and Sabatini, B., J. Neurosci., 2014, vol. 34, no. 25, pp. 8557–8569.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hoebel, B.G., Avena, N., and Rada, M.P., Curr. Opin. Pharmacol., 2007, vol. 7, no. 6, pp. 617–627.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V., and Di Filippo, M., Nat. Neurosci., 2014, vol. 17, no. 8, pp. 1022–1030.CrossRefPubMedGoogle Scholar
  16. 16.
    Aosaki, T., Miura, M., Takeo-Suzuki, T., Nishimura, K., and Masuda, M. Geriatr. Gerontol. Int., 2010, vol. 10, pp. S148–S157.CrossRefPubMedGoogle Scholar
  17. 17.
    Gonzales, K.K., Ann. NY Acad. Sci., 2015, vol. 1349, pp. 1–45.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Aosaki, T., Miura, M., and Masuda, M. Brain Nerve, 2009, vol. 61, no. 4, pp. 373–380.PubMedGoogle Scholar
  19. 19.
    Lester, D.B., Rogers, T.D., and Blaha, C.D., CNS Neurosci. Ther., 2010, vol. 16, no. 3, pp. 137–162.CrossRefPubMedGoogle Scholar
  20. 20.
    Brock, M., Nickel, A.C., Madziar, B., Blusztajn, J.K., and Berse, B., Brain Res., 2007, vol. 1145, pp. 1–10.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kuhl, D.E., Minoshima, S., Fessler, J.A., Frey, K.A., Foster, N.L., Ficaro, E.P., Wieland, D.M., and Koeppe, R.A., Ann. Neurol., 1996, vol. 40, no. 3, pp. 399–410.CrossRefPubMedGoogle Scholar
  22. 22.
    Glowinski, J. and Iversen, L.L., J. Neurochem., 1966, vol. 13, no. 8, pp. 655–669.CrossRefPubMedGoogle Scholar
  23. 23.
    Messripour, M. and Clark, J.B., J. Neurochem., 1982, vol. 38, no. 4, pp. 1139–1143.CrossRefPubMedGoogle Scholar
  24. 24.
    Ellman, G.L., Courtney, D.K., Andreas, V., and Featherstone, R.M., Biochem. Pharmacol., 1961, vol. 7, pp. 88–95.CrossRefPubMedGoogle Scholar
  25. 25.
    Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J., J. Biol. Chem., 1951, vol. 193, no. 1, pp. 265–275.PubMedGoogle Scholar
  26. 26.
    Baranyi, M., Porceddu, P., Gölöncsér, F., Kulcsár, S., Otrokocsi, L., Kittel, Á., Pinna, A., Frau, L., Huleatt, P.B., Khoo, M.L., Chai, C.L., Dunkel, P., Mátyus, P., Morelli, M., and Sperlágh, B., Mol. Neurodegener., 2016, vol. 11, no. 6, pp. 1–22.Google Scholar
  27. 27.
    Messripour, M. and Clark, J.B., Neurochem. Int., 1985, vol. 7, no. 5, pp. 811–818.CrossRefPubMedGoogle Scholar
  28. 28.
    Daubner, S.C., Le, T., and Wang, S., Arch. Biochem. Biophys., 2011, vol. 508, no. 1, pp. 1–12.CrossRefPubMedGoogle Scholar
  29. 29.
    Heikkila, R.E., Manzino, L., and Cabbat, F.S., Nature, 1984, vol. 311, no. 5985, pp. 467–469.CrossRefPubMedGoogle Scholar
  30. 30.
    Okada, M., Nakao, R., Hosoi, R., Zhang, M.R., Fukumura, T., Suzuki, K., and Inoue, O., J. Cerebral Blood Flow Metabol., 2011, vol. 31, no. 1, pp. 124–131.CrossRefGoogle Scholar
  31. 31.
    Lindgren, N., Xu, Z.Q., Herrera-Marschitz, M., Haycock, J., Hökfelt, T., and Fisone, G., Eur. J. Neurosci., 2001, vol. 13, no. 4, pp. 773–780.CrossRefPubMedGoogle Scholar
  32. 32.
    Dreyer, J.K., J. Neurosci., 2014, vol. 34, no. 37, pp. 12444–12456.CrossRefPubMedGoogle Scholar
  33. 33.
    Zhang, D., Mallela, A., Sohn, D., Carroll, F.I., Bencherif, M., Letchworth, S., and Quik, M., J. Pharmacol. Exp. Ther., 2013, vol. 347, no. 1, pp. 225–234.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Freeze, B.S., Kravitz, A.V., Hammack, N., Berke, J.D., and Kreitzer, A.C., J. Neurosci., 2013, vol. 33, no. 47, pp. 18531–18539.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Pignatelli, M. and Bonci, A., Neuron, 2015, vol. 86, vol. 5, pp. 1145–1157.CrossRefPubMedGoogle Scholar
  36. 36.
    Santangelo, G., Barone, P., Trojano, L., and Vitale, C., Parkinson. Rel. Disord., 2013, vol. 19, no. 7, pp. 645–653.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Department of Clinical Biochemistry, Isfahan (Khorasgan) BranchIslamic Azad UniversityArghavanieh, Khorasgan, IsfahanIran
  2. 2.Department of Chemistry, Isfahan (Khorasgan) BranchIslamic Azad UniversityIsfahanIran
  3. 3.Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran

Personalised recommendations