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Potential of a planarian model to study certain aspects of anti-Parkinsonism drugs

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DOI: 10.4236/apd.2013.23014    4,189 Downloads   6,891 Views   Citations

ABSTRACT

We previously created and investigated a planarian model for the study of drug action, abuse, physical dependence, receptor affinity, the toxicity of heavy metals in wastewater, and seizures. For the present pilot study, we investigated the possibility that this model might be useful for studying certain aspects of drugs used in treatment of Parkinson disease. For the first step, we were interested in finding an in vivo metric for the inhibition of L-DOPA by an inhibitor of DOPA decarboxylase. The direct clinical relevance of the endpoint was of secondary concern during this preliminary phase of model development. Two metrics were explored: L-DOPA-induced inhibition of motility (locomotor velocity) and dopamine-mediated toxicity, which was quantified using a Kaplan-Meier survival curve. L-DOPA produced both dose- and time-related toxicity. The water-soluble DOPA decarboxylase inhibitor benserazide dose-dependently inhibited the effect of L-DOPA, as manifested by a leftward shift in the Kaplan-Meier curve. Additional work was initiated using the more sensitive and a graded metric of spontaneous locomotor velocity. The encouraging results of this pilot study suggest that: 1) planarians contain DOPA decarboxylase or an equivalent enzyme, and 2) the planarian model might be useful for the study of certain aspects of anti-Parkinsonism pharmacotherapy.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Raffa, R. , Danah, J. , Tallarida, C. , Zimmerman, C. , Gill, G. , Baron, S. and Rawls, S. (2013) Potential of a planarian model to study certain aspects of anti-Parkinsonism drugs. Advances in Parkinson's Disease, 2, 70-74. doi: 10.4236/apd.2013.23014.

References

[1] Dauer, W. and Przedborski, S. (2003) Parkinson’s disease: Mechanisms and models. Neuron, 39, 889-909. doi:10.1016/S0896-6273(03)00568-3
[2] Garcia Ruiz, P.J., Catalan, M.J. and Fernandez Carril, J. (2011) Initial motor symptoms of Parkinson disease. Neurologist, 17, S18-S20. doi:10.1097/NRL.0b013e31823966b4
[3] Lees, A.J., Hardy, J. and Revesz, T. (2009) Parkinson’s disease. Lancet, 373, 2055-2066. doi:10.1016/S0140-6736(09)60492-X
[4] Hughes, A.J., Daniel, S.E., Kilford, L. and Lees, A.J. (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. Journal of Neurol Neurosurg Psychiatry, 55, 181-184. doi:10.1136/jnnp.55.3.181
[5] De Lau, L.M., Koudstaal, P.J., Hofman, A. and Breteler, M.M. (2006) Subjective complaints precede Parkinson disease: The rotterdam study. Archives of Neurology, 63, 362-365. doi:10.1001/archneur.63.3.noc50312
[6] Shahed, J. and Jankovic, J. (2007) Motor symptoms in Parkinson’s disease. Handbook of Clinical Neurology, 83, 329-342. doi:10.1016/S0072-9752(07)83013-2
[7] Hoehn, M.M. and Yahr, M.D. (1967) Parkinsonism: Onset, progression and mortality. Neurology, 17, 427-442. doi:10.1212/WNL.17.5.427
[8] De Rijk, M.C., Breteler, M.M., Graveland, G.A., Ott, A., Grobbee, D.E., van der Meche, F.G. and Hofman, A. (1995) Prevalence of Parkinson’s disease in the elderly: The Rotterdam study. Neurology, 45, 2143-2146. doi:10.1212/WNL.45.12.2143
[9] De Lau, L.M. and Breteler, M.M. (2006) Epidemiology of Parkinson’s disease. The Lancet Neurology, 5, 525-535. doi:10.1016/S1474-4422(06)70471-9
[10] Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K. and Seitelberger, F. (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. Journal of the Neurological Sciences, 20, 415-455. doi:10.1016/0022-510X(73)90175-5
[11] Gilgun-Sherki, Y., Hellmann, M., Melamedm E., and Offen, D. (2004) The role of neurotransmitters and neuropeptides in Parkinson’s disease: Implications for therapy. Drugs of the Future, 29, 1261. doi:10.1358/dof.2004.029.12.869227
[12] Trugman, J. M. and James, C. L. (1992) Rapid development of dopaminergic supersensitivity in reserpinetreated rats demonstrated with 14C-2-deoxyglucose autoradiography. The Journal of Neuroscience, 12, 2875-2879.
[13] Huse, D.M., Castelli-Haley, J., Orsini, L.S., Lenhart G. and Abdalla, J.A. (2006) Patterns of initial pharmaco-therapy for Parkinson’s disease in the United States. Journal of Geriatric Psychiatry and Neurology, 19, 91-97. doi:10.1177/0891988706286512
[14] Hornykiewicz, O. (2002) L-DOPA: From a biologically inactive amino acid to a successful therapeutic agent. Amino Acids, 23, 65-70. doi:10.1007/s00726-001-0111-9
[15] Wade, L.A. and Katzman, R. (1975) Synthetic amino acids and the nature of L-DOPA transport at the bloodbrain barrier. Journal of Neurochemistry, 25, 837-842. doi:10.1111/j.1471-4159.1975.tb04415.x
[16] Melamed, E., Hefti, F., Pettibone, D.J., Liebman, J. and Wurtman, R.J. (1981) Aromatic L-amino acid decarboxylase in rat corpus striatum: Implications for action of L-dopa in Parkinsonism. Neurology, 31, 651-655. doi:10.1212/WNL.31.6.651
[17] Algeri, S., Carolei, A., Ferretti, P., Gallone, C., Palladini, G. and Venturini, G. (1983) Effects of dopaminergic agents on monoamine levels and motor behaviour in planaria. Comparative Biochemistry and Physiology Part C, 74, 27-29. doi:10.1016/0742-8413(83)90142-1
[18] Buttarelli, F.R., Pontieri, F.E., Margotta, V. and Palladini, G. (2000) Acetylcholine/dopamine interaction in planaria. Comparative Biochemistry and Physiology Part C, 125, 225-231.
[19] Carolei, A., Margotta, V. andPalladini, G. (1975) Proposal of a new model with dopaminergic-cholinergic interactions for neuropharmacological investigations. Neuro-psychobiology, 1, 355-364. doi:10.1159/000117512
[20] Palladini, G., Margotta, V., Carolei, A., Chiarini, F., Del Piano, M., Lauro, G.M., Medolago-Albani, L. and Venturini, G. (1983) The cerebrum of Dugesia gonocephala s.1. Platyhelminthes, Turbellaria, Tricladida. Morphological and functional observations. Journal für Hirnforschung, 24, 165-172
[21] Palladini, G., Ruggeri, S., Stocchi, F., De Pandis, M.F., Venturini, G. and Margotta, V. (1996) A pharmacological study of cocaine activity in planaria. Comparative Biochemistry and Physiology Part C, 115, 41-45. doi:10.1016/S0742-8413(96)00053-9
[22] Passarelli, F., Merante, A., Pontieri, F.E., Margotta, V., Venturini, G. and Palladini, G. (1999) Opioid-dopamine interaction in planaria: A behavioral study. Comparative Biochemistry and Physiology Part C, 124, 51-55. doi:10.1016/S0742-8413(99)00048-1
[23] Ribeiro, P., El-Shehabi, F. and Patocka, N. (2005) Classical transmitters and their receptors in flatworms. Parasitology, 131, S19-40. doi:10.1017/S0031182005008565
[24] Venturini, G., Carolei, A., Palladini, G., Margotta, V. and Lauro, M.G. (1983) Radioimmunological and immunocytochemical demonstration of Met-enkephalin in planaria. Comparative Biochemistry and Physiology Part C, 74, 23-25. doi:10.1016/0742-8413(83)90141-X
[25] Venturini, G., Stocchi, F., Margotta, V., Ruggieri, S., Bravi, D., Bellantuono, P. and Palladini, G. (1989) A pharmacological study of dopaminergic receptors in planaria. Neuropharmacology, 28, 1377-1382. doi:10.1016/0028-3908(89)90013-0
[26] Welsh, J.H. and Williams, L.D. (1970) Monoamine-containing neurons in planaria. Journal of Comparative Neurology, 138, 103-115. doi:10.1002/cne.901380108
[27] Raffa, R.B. and Desai, P. (2005) Description and quantification of cocaine withdrawal signs in Planaria. Brain Research, 1032, 200-202. doi:10.1016/j.brainres.2004.10.052
[28] Raffa, R.B., Finno, K.E., Tallarida, C.S. and Rawls, S.M. (2010) Topiramate-antagonism of L-glutamate-induced paroxysms in planarians. European Journal of Pharmacology, 649, 150-153. doi:10.1016/j.ejphar.2010.09.021
[29] Raffa, R.B., Holland, L.J. and Schulingkamp R.J. (2001) Quantitative assessment of dopamine D2 antagonist activity using invertebrate (Planaria) locomotion as a functional endpoint. Journal of Pharmacological and Toxicological Methods, 45, 223-226. doi:10.1016/S1056-8719(01)00152-6
[30] Raffa, R.B. and Martley, A.F. (2005) Amphetamine-induced increase in planarian locomotor activity and block by UV light. Brain Research, 1031, 138-140. doi:10.1016/j.brainres.2004.10.051
[31] Raffa, R.B. and Rawls, S.M. (2008) Planaria: A Model for Drug Action and Abuse. Landes Bioscience.
[32] Raffa, R.B., Robinson, M.J. and Tallarida, R.J. (1985) Ultraviolet light-induced photorelaxation of agonist-contracted rabbit aorta: Further characterization and the estimation of drug-receptor rate constants. Drug Development Research, 5, 359-369. doi:10.1002/ddr.430050409
[33] Raffa, R.B., Stagliano, G.W. and Umeda, S. (2003) Kappa-opioid withdrawal in Planaria. Neuroscience Letters, 349, 139-142. doi:10.1016/S0304-3940(03)00814-0
[34] Raffa, R.B. andValdez, J.M. (2001) Cocaine withdrawal in Planaria. European Journal of Pharmacology, 430, 143-145. doi:10.1016/S0014-2999(01)01358-9
[35] Raffa, R.B., Valdez, J.M., Holland, L.J. and Schulingkamp, R.J. (2000) Energy-dependent UV light-induced disruption of (-)sulpiride antagonism of dopamine. European Journal of Pharmacology, 406, R11-R12. doi:10.1016/S0014-2999(00)00730-5
[36] Rawls, S.M., Thomas, T., Adeola, M., Patil, T., Raymondi, N., Poles, A., Loo, M. and Raffa, R.B. (2009) Topiramate antagonizes NMDA- and AMPA-induced seizure-like activity in planarians. Pharmacology Biochemistry and Behavior, 93, 363-367. doi:10.1016/j.pbb.2009.05.005
[37] Umeda, S., Stagliano, G.W. and Raffa, R.B. (2004) Cocaine and kappa-opioid withdrawal in Planaria blocked by D-, but not L-, glucose. Brain Reseatch, 1018, 181-185. doi:10.1016/j.brainres.2004.05.057
[38] Pagan, O.R., Baker, D., Deats, S., Montgomery, E., Tenaglia, M., Randolph, C., Kotturu, D., Tallarida, C., Bach, D., Wilk, G., Rawlsm S. and Raffa, R.B. (2012) Planarians in pharmacology: Parthenolide is a specific behavioral antagonist of cocaine in the planarian Girardia tigrina. The International Journal of Developmental Biology, 56, 193-196. doi:10.1387/ijdb.113486op
[39] Pagan, O.R., Eterovic, V.A., Garcia, M., Vergne, D., Basilio, C.M., Rodriguez, A.D. and Hann, R.M. (2001) Cembranoid and long-chain alkanol sites on the nicotinic acetylcholine receptor and their allosteric interaction. Biochemistry, 40, 11121-11130. doi:10.1021/bi0112255
[40] Pagan, O.R., Rowlands, A.L., Azam, M., Urban, K.R., Bidja, A.H., Roy, D.M., Feeney, R.B. and Afshari, L.K. (2008) Reversal of cocaine-induced planarian behavior by parthenolide and related sesquiterpene lactones. Pharmacology Biochemistry and Behavior, 89, 160-170. doi:10.1016/j.pbb.2007.12.008
[41] Pagan, O.R., Rowlands, A.L., Fattore, A.L., Coudron, T., Urban, K.R., Bidja, A.H. and Eterovic, V.A. (2009) A cembranoid from tobacco prevents the expression of nicotine-induced withdrawal behavior in planarian worms. European Journal of Pharmacology, 615, 118-124. doi:10.1016/j.ejphar.2009.05.022
[42] Pagan, O.R., Rowlands, A.L. and Urban, K.R. (2006) Toxicity and behavioral effects of dimethylsulfoxide in planaria. Neuroscience Letters, 407, 274-278. doi:10.1016/j.neulet.2006.08.073
[43] Pagan, O.R., Sivaprakasam, K. and Oswald, R.E. (2007) Molecular properties of local anesthetics as predictors of affinity for nicotinic acetylcholine receptors. Journal of Neuroscience Research, 85, 2943-2949. doi:10.1002/jnr.21402
[44] Nishimura, K., Kitamura, Y., Inoue, T., Umesono, Y., Sano, S., Yoshimoto, K., Inden, M., Takata, K., Taniguchi, T., Shimohama, S. and Agata, K. (2007) Reconstruction of dopaminergic neural network and locomotion function in planarian regenerates. Developmental Neurobiology, 67, 1059-1078. doi:10.1002/dneu.20377

  
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