Presynaptic effects of levodopa and their possible role in dyskinesia

Movement Disorders

Volumn 30, Issue 1, 2015, Pages 45-53

  Mosharov, Eugene V ^a   Borgkvist, Anders ^a   Sulzer, David ^a  

^a Department of Medicine   (United States)

Author keywords

Dopamine; Dyskinesia; Levodopa; Parkinson's Disease; Presynaptic; Serotonin

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; 3,4 DIHYDROXYPHENYLACETIC ACID; CATECHOL DERIVATIVE; COCAINE; DOPAMINE; DOPAMINE TRANSPORTER; LEVODOPA; METHAMPHETAMINE; NEUROTRANSMITTER; SEROTONIN; TETRODOTOXIN; DOPAMINE RECEPTOR STIMULATING AGENT;

BASAL GANGLION; BRAIN REGION; CYTOSOL; DOPAMINE RELEASE; DOPAMINERGIC TRANSMISSION; DRUG EFFICACY; DRUG SAFETY; DYSKINESIA; HIPPOCAMPUS; HUMAN; LEVODOPA INDUCED DYSKINESIA; MESENCEPHALON; MOTOR PERFORMANCE; NEUROTRANSMISSION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PC12 CELL LINE; PRESYNAPTIC NERVE; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SEROTONINERGIC NERVE CELL; SYNAPSE VESICLE; ANIMAL; CYTOLOGY; DRUG EFFECTS; DYSKINESIA, DRUG-INDUCED; METABOLISM; NERVE CELL; NERVE ENDING; PATHOLOGY;

ANIMALS; DOPAMINE; DOPAMINE AGENTS; DYSKINESIA, DRUG-INDUCED; HUMANS; LEVODOPA; NEURONS; PARKINSON DISEASE; PRESYNAPTIC TERMINALS;

EID: 84940449100     PISSN: 08853185     EISSN: 15318257     Source Type: Journal    
DOI: 10.1002/mds.26103     Document Type: Review

References (114)

1. Birkmayer W, Hornykiewicz O. Der L-3, 4-dioxyphenylalanin (DOPA) Effekt bei der Parkinson-akinesia (Effect of L-3, 4-dioxyphenylalanine (DOPA) on Parkinson's disease akinesia.). Wien Klin Wochenschr 1961;73:787-788.
2. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967;276:374-379.
3. Ramsey AJ, Fitzpatrick PF. Effects of phosphorylation on binding of catecholamines to tyrosine hydroxylase: specificity and thermodynamics. Biochemistry 2000;39:773-778.
4. Hadjiconstantinou M, Neff NH. Enhancing aromatic L-amino acid decarboxylase activity: implications for L-DOPA treatment in Parkinson's disease. CNS Neurosci Ther 2008;14:340-351.
5. Wolf ME, Roth RH. Autoreceptor regulation of dopamine synthesis. Ann N Y Acad Sci 1990;604:323-343.
6. Lindgren N, Xu ZQ, Herrera-Marschitz M, Haycock J, Hökfelt T, Fisone G. Dopamine D(2) receptors regulate tyrosine hydroxylase activity and phosphorylation at Ser40 in rat striatum. Eur J Neurosci 2001;13:773-780.
7. Peter D, Liu Y, Sternini C, de Giorgio R, Brecha N, Edwards RH. Differential expression of two vesicular monoamine transporters. J Neurosci 1995;15:6179-6188.
8. Weihe E, Schäfer MK, Erickson JD, Eiden LE. Localization of vesicular monoamine transporter isoforms (VMAT1 and VMAT2) to endocrine cells and neurons in rat. J Mol Neurosci 1994;5:149-164.
9. Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci U S A 1996;93:5166-5171.
10. Wimalasena K. Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry. Med Res Rev 2011;31:483-519.
11. Guillot TS, Miller GW. Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons. Mol Neurobiol 2009;39:149-170.
12. Sames D, Dunn M, Karpowicz RJ, Jr., Sulzer D. Visualizing neurotransmitter secretion at individual synapses. ACS chemical neuroscience 4, 648-651, doi:10.1021/cn4000956 (2013).
13. Zoli M, Jansson A, Sykova E, Agnati LF, Fuxe K. Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol Sci 1999;20:142-150.
14. Sulzer D, Pothos EN. Regulation of quantal size by presynaptic mechanisms. Rev Neurosci 2000;11:159-212.
15. Nirenberg MJ, Chan J, Liu Y, Edwards RH, Pickel VM. Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain dopaminergic neurons: potential sites for somatodendritic storage and release of dopamine. J Neurosci 1996;16:4135-4145.
16. Pickel VM, Nirenberg MJ, Milner TA. Ultrastructural view of central catecholaminergic transmission: immunocytochemical localization of synthesizing enzymes, transporters and receptors. J Neurocytol 1996;25:843-856.
17. Jones SR, Gainetdinov RR, Jaber M, Giros B, Wightman RM, Caron MG. Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proc Natl Acad Sci U S A 1998;95:4029-4034.
18. Sulzer D. How addictive drugs disrupt presynaptic dopamine neurotransmission. Neuron 2011;69:628-649.
19. Freund TF, Powell JF, Smith AD. Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines. Neuroscience 1984;13:1189-1215.
20. Venton BJ, Zhang H, Garris PA, Phillips PE, Sulzer D, Wightman RM. Real-time decoding of dopamine concentration changes in the caudate-putamen during tonic and phasic firing. J Neurochem 2003;87:1284-1295.
21. Vieira-Coelho MA, Soares-Da-Silva P. Uptake and intracellular fate of L-DOPA in a human intestinal epithelial cell line: Caco-2. Am J Physiol 1998;275:C104-C112.
22. Mosharov EV, Larsen KE, Kanter E, et al. Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons. Neuron 2009;62:218-229.
23. Mosharov EV, Staal RG, Bové J, et al. Alpha-synuclein overexpression increases cytosolic catecholamine concentration. J Neurosci 2006;26:9304-9311.
24. Wightman RM, Jankowski JA, Kennedy RT, et al. Temporally resolved catecholamine spikes correspond to single vesicle release from individual chromaffin cells. Proc Natl Acad Sci U S A 1991;88:10754-10758.
25. Pothos EN, Davila V, Sulzer D. Presynaptic recording of quanta from midbrain dopamine neurons and modulation of the quantal size. J Neurosci 1998;18:4106-4118.
26. Staal RG, Mosharov EV, Sulzer D. Dopamine neurons release transmitter via a flickering fusion pore. Nat Neurosci 2004;7:341-346.
27. Gong LW, Hafez I, Alvarez de Toledo G, Lindau M. Secretory vesicles membrane area is regulated in tandem with quantal size in chromaffin cells. J Neurosci 2003;23:7917-7921.
28. Pothos E, Desmond M, Sulzer D. L-3, 4-dihydroxyphenylalanine increases the quantal size of exocytotic dopamine release in vitro. J Neurochem 1996;66:629-636.
29. Colliver TL, Hess EJ, Pothos EN, Sulzer D, Ewing AG. Quantitative and statistical analysis of the shape of amperometric spikes recorded from two populations of cells. J Neurochem 2000;74:1086-1097.
30. Omiatek DM, Bressler AJ, Cans AS, Andrews AM, Heien ML, Ewing AG. The real catecholamine content of secretory vesicles in the CNS revealed by electrochemical cytometry. Sci Rep 2013;3:1447.
31. Omiatek DM, Dong Y, Heien ML, Ewing AG. Only a fraction of quantal content is released during exocytosis as revealed by electrochemical cytometry of secretory vesicles. ACS Chem Neurosci 2010;1:234-245.
32. Burke RE, O'Malley K. Axon degeneration in Parkinson's disease. Exp Neurol 2013;246:72-83.
33. Abercrombie ED, Bonatz AE, Zigmond MJ. Effects of L-dopa on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats. Brain Res 1990;525:36-44.
34. Lee J, Zhu WM, Stanic D, et al. Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia. Brain 2008;131:1574-1587.
35. Zigmond MJ. Do compensatory processes underlie the preclinical phase of neurodegenerative disease? Insights from an animal model of parkinsonism. Neurobiol Dis 1997;4:247-253.
36. Rice ME, Cragg SJ. Dopamine spillover after quantal release: rethinking dopamine transmission in the nigrostriatal pathway. Brain Res Rev 2008;58:303-313.
37. Schmitz Y, Lee CJ, Schmauss C, Gonon F, Sulzer D. Amphetamine distorts stimulation-dependent dopamine overflow: effects on D2 autoreceptors, transporters, and synaptic vesicle stores. J Neurosci 2001;21:5916-5924.
38. Miller DW, Abercrombie ED. Role of high-affinity dopamine uptake and impulse activity in the appearance of extracellular dopamine in striatum after administration of exogenous L-DOPA: studies in intact and 6-hydroxydopamine-treated rats. J Neurochem 1999;72:1516-1522.
39. Sarre S, De Klippel N, Herregodts P, Ebinger G, Michotte Y. Biotransformation of locally applied L-dopa in the corpus striatum of the hemi-parkinsonian rat studied with microdialysis. Naunyn Schmiedebergs Arch Pharmacol 1994;350:15-21.
40. Weintraub D, Nirenberg MJ. Impulse control and related disorders in Parkinson's disease. Neurodegener Dis 2013;11:63-71.
41. Duan H, Wang J. Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther 2010;335:743-753.
42. Sader-Mazbar O, Loboda Y, Rabey MJ, Finberg JP. Increased L-DOPA-derived dopamine following selective MAO-A or -B inhibition in rat striatum depleted of dopaminergic and serotonergic innervation. Br J Pharmacol 2013;170:999-1013.
43. Larsen MB, Sonders MS, Mortensen OV, Larson GA, Zahniser NR, Amara SG. Dopamine transport by the serotonin transporter: a mechanistically distinct mode of substrate translocation. J Neurosci 2011;31:6605-6615.
44. Schmitz Y, Schmauss C, Sulzer D. Altered dopamine release and uptake kinetics in mice lacking D2 receptors. J Neurosci 2002;22:8002-8009.
45. Navailles S, Lagiere M, Contini A, De Deurwaerdere P. Multisite intracerebral microdialysis to study the mechanism of L-DOPA induced dopamine and serotonin release in the parkinsonian brain. ACS Chem Neurosci 2013;4:680-692.
46. Porras G, De Deurwaerdere P, Li Q, et al. L-dopa-induced dyskinesia: beyond an excessive dopamine tone in the striatum. Sci Rep 2014;4:3730.
47. Sulzer D, Bogulavsky J, Larsen KE, et al. Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci U S A 2000;97:11869-11874.
48. Zucca FA, Basso E, Cupaioli FA, Ferrari E, Sulzer D, Casella L, Zecca L. Neuromelanin of the human substantia nigra: an update. Neurotox Res 2014;25:13-23.
49. Cebrián C, Zucca FA, Mauri P, et al. MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration. Nat Commun 2014;5:3633.
50. Surmeier DJ, Guzman JN, Sanchez-Padilla J, Goldberg JA. What causes the death of dopaminergic neurons in Parkinson's disease? Prog Brain Res 2010;183:59-77.
51. Hetzenauer A, Sinnegger-Brauns MJ, Striessnig J, Singewald N. Brain activation pattern induced by stimulation of L-type Ca2+-channels: contribution of Ca(V)1.3 and Ca(V)1.2 isoforms. Neuroscience 2006;139:1005-1015.
52. Stansley BJ, Yamamoto BK. L-dopa-induced dopamine synthesis and oxidative stress in serotonergic cells. Neuropharmacology 2013;67:243-251.
53. Edwards RH. Neural degeneration and the transport of neurotransmitters. Ann Neurol 1993;34:638-645.
54. Gainetdinov RR, Fumagalli F, Wang YM, Jones SR, Levey AI, Miller GW, Caron MG. Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J Neurochem 1998;70:1973-1978.
55. Lotharius J, Brundin P. Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum Mol Genet 2002;11:2395-2407.
56. Uhl GR. Hypothesis: the role of dopaminergic transporters in selective vulnerability of cells in Parkinson's disease. Ann Neurol 1998;43:555-560.
57. Pifl C, Rajput A, Reither H, et al. Is Parkinson's disease a vesicular dopamine storage disorder? Evidence from a study in isolated synaptic vesicles of human and nonhuman primate striatum. J Neurosci 2014;34:8210-8218.
58. Lohr KM, Bernstein AI, Stout KA, et al. Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo. Proc Natl Acad Sci U S A 2014;111:9977-9982.
59. Blaschko H. Amine oxidase and amine metabolism. Pharmacol Rev 1952;4:415-458.
60. Burke WJ, Li SW, Chung HD, et al. Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases. Neurotoxicology 2004;25:101-115.
61. Goldstein DS, Kopin IJ, Sharabi Y. Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders. Pharmacol Ther 2014 Jun 16. pii: S0163-7258(14)00123-5. doi: 10.1016/j.pharmthera.2014.06.006. [Epub ahead of print].
62. Caudle WM, Richardson JR, Wang MZ, et al. Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci. 2007;27:8138-8148.
63. Hastings TG, Berman SB. Dopamine-induced toxicity and quinone modification. In: Creveling CR, ed. Role of Catechol Quinone Species in Cellular Toxicity. Johnson City, TN: F.P. Graham; 1999: 69-89.
64. Larsen KE, Fon EA, Hastings TG, Edwards RH, Sulzer D. Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. J Neurosci 2002;22:8951-8960.
65. Fon EA, Pothos EN, Sun BC, Killeen N, Sulzer D, Edwards RH. Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action. Neuron 1997;19:1271-1283.
66. Nutt JG. Clinical pharmacology of levodopa-induced dyskinesia. Ann Neurol 2000;47(4 Suppl 1):S160-S164; discussion, S164-S166.
67. Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 2001;16:448-458.
68. Fahn S. The spectrum of levodopa-induced dyskinesias. Ann Neurol 2000;47(4 Suppl 1):S2-S9; discussion, S9-S11.
69. Cenci MA, Lundblad M. Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia. J Neurochem 2006;99:381-392.
70. Bargiotas P, Konitsiotis S. Levodopa-induced dyskinesias in Parkinson's disease: emerging treatments. Neuropsychiatr Dis Treat 2013;9:1605-1617.
71. Olanow CW, Agid Y, Mizuno Y, et al. Levodopa in the treatment of Parkinson's disease: current controversies. Mov Disord 2004;19:997-1005.
72. Olanow CW, Obeso JA, Stocchi F. Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications. Lancet Neurol 2006;5:677-687.
73. Olanow CW, Kieburtz K, Odin P, et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014;13:141-149.
74. Iderberg H, Francardo V, Pioli EY. Animal models of L-DOPA-induced dyskinesia: an update on the current options. Neuroscience 2012;211:13-27.
75. Huot P, Johnston TH, Koprich JB, Fox SH, Brotchie JM. The pharmacology of L-DOPA-induced dyskinesia in Parkinson's disease. Pharmacol Rev 2013;65:171-222.
76. Zhuang X, Mazzoni P, Kang UJ. The role of neuroplasticity in dopaminergic therapy for Parkinson disease. Nat Rev Neurol 2013;9:248-256.
77. Cenci MA, Konradi C. Maladaptive striatal plasticity in L-DOPA-induced dyskinesia. Prog Brain Res 2010;183:209-233.
78. Heiman M, Heilbut A, Francardo V, et al. Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia. Proc Natl Acad Sci U S A 2014;111:4578-4583.
79. Carta M, Bezard E. Contribution of pre-synaptic mechanisms to L-DOPA-induced dyskinesia. Neuroscience 2011;198:245-251.
80. Tedroff J, Pedersen M, Aquilonius SM, Hartvig P, Jacobsson G, Långström B. Levodopa-induced changes in synaptic dopamine in patients with Parkinson's disease as measured by [11C]raclopride displacement and PET. Neurology 1996;46:1430-1436.
81. Pavese N, Evans AH, Tai YF, Hotton G, Brooks DJ, Lees AJ, Piccini P. Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study. Neurology 2006;67:1612-1617.
82. de la Fuente-Fernández R, Sossi V, Huang Z, et al. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias. Brain 2004;127:2747-2754.
83. Meissner W, Ravenscroft P, Reese R, et al. Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracellular striatal dopamine. Neurobiol Dis 2006;22:586-598.
84. Lindgren HS, Andersson DR, Lagerkvist S, Nissbrandt H, Cenci MA. L-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson's disease: temporal and quantitative relationship to the expression of dyskinesia. J Neurochem 2010;112:1465-1476.
85. Ulusoy A, Sahin G, Kirik D. Presynaptic dopaminergic compartment determines the susceptibility to L-DOPA-induced dyskinesia in rats. Proc Natl Acad Sci U S A 2010;107:13159-13164.
86. Pons R, Syrengelas D, Youroukos S, et al. Levodopa-induced dyskinesias in tyrosine hydroxylase deficiency. Mov Disord 2013;28:1058-1063.
87. Sulzer D, Surmeier DJ. Neuronal vulnerability, pathogenesis, and Parkinson's disease. Mov Disord 2013;28:41-50.
88. Rylander D, Rylander D, Parent M, O'Sullivan SS, et al. Maladaptive plasticity of serotonin axon terminals in levodopa-induced dyskinesia. Ann Neurol 2010;68:619-628.
89. Butcher L, Engel J, Fuxe K. L-dopa induced changes in central monoamine neurons after peripheral decarboxylase inhibition. J Pharm Pharmacol 1970;22:313-316.
90. Tanaka H, Kannari K, Maeda T, Tomiyama M, Suda T, Matsunaga M. Role of serotonergic neurons in L-DOPA-derived extracellular dopamine in the striatum of 6-OHDA-lesioned rats. Neuroreport 1999;10:631-634.
91. Navailles S, Bioulac B, Gross C, De Deurwaerdere P. Serotonergic neurons mediate ectopic release of dopamine induced by L-DOPA in a rat model of Parkinson's disease. Neurobiol Dis 2010;38:136-143.
92. Lopez A, Munoz A, Guerra MJ, Labandeira-Garcia JL. Mechanisms of the effects of exogenous levodopa on the dopamine-denervated striatum. Neuroscience 2001;103:639-651.
93. Kannari K, Tanaka H, Maeda T, Tomiyama M, Suda T, Matsunaga M. Reserpine pretreatment prevents increases in extracellular striatal dopamine following L-DOPA administration in rats with nigrostriatal denervation. J Neurochem 2000;74:263-269.
94. Maeda T, Kannari K, Suda T, Matsunaga M. Loss of regulation by presynaptic dopamine D2 receptors of exogenous L-DOPA-derived dopamine release in the dopaminergic denervated striatum. Brain Res 1999;817:185-191.
95. Arai R, Karasawa N, Geffard M, Nagatsu T, Nagatsu, I. Immunohistochemical evidence that central serotonin neurons produce dopamine from exogenous L-DOPA in the rat, with reference to the involvement of aromatic L-amino acid decarboxylase. Brain Res 1994;667:295-299.
96. Yamada H, Aimi Y, Nagatsu I, Taki K, Kudo M, Arai R. Immunohistochemical detection of L-DOPA-derived dopamine within serotonergic fibers in the striatum and the substantia nigra pars reticulata in Parkinsonian model rats. Neurosci Res 2007;59:1-7.
97. Melamed E, Hefti F, Liebman J, Schlosberg AJ, Wurtman RJ. Serotonergic neurones are not involved in action of L-dopa in Parkinson's disease. Nature 1980;283:772-774.
98. Ng KY, Chase TN, Colburn RW, Kopin IJ. Dopamine: stimulation-induced release from central neurons. Science 1971;172:487-489.
99. Nevalainen N, Af Bjerken S, Gerhardt GA, Stromberg I. Serotonergic nerve fibers in L-DOPA-derived dopamine release and dyskinesia. Neuroscience 2014;260:73-86.
100. Everett GM, Borcherding JW. L-dopa: effect on concentrations of dopamine, norepinephrine, and serotonin in brains of mice. Science 1970;168:849-850.
101. Miguelez C, Morera-Herreras T, Torrecilla M, Ruiz-Ortega JA, Ugedo L. Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease. Front Neural Circuits 2014;8:21.
102. Navailles S, Bioulac B, Gross C, De Deurwaerdere P. Chronic L-DOPA therapy alters central serotonergic function and L-DOPA-induced dopamine release in a region-dependent manner in a rat model of Parkinson's disease. Neurobiol Dis 2011;41:585-590.
103. Yanovsky Y, Li S, Klyuch BP, et al. L-Dopa activates histaminergic neurons. J Physiol 2011;589:1349-1366.
104. Carta M, Tronci E. Serotonin system implication in l-DOPA-induced dyskinesia: from animal models to clinical investigations. Front Neurol 2014;5:78.
105. Carta M, Carlsson T, Kirik D, Bjorklund A. Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain 2007;130:1819-1833.
106. Eskow KL, Dupre KB, Barnum CJ, Dickinson SO, Park JY, Bishop C. The role of the dorsal raphe nucleus in the development, expression, and treatment of L-dopa-induced dyskinesia in hemiparkinsonian rats. Synapse 2009;63:610-620.
107. Tomiyama M, Kimura T, Maeda T, Kannari K, Matsunaga M, Baba M. A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to L-DOPA in a rodent model of Parkinson's disease. Neurosci Res 2005;52:185-194.
108. Muñoz A, Carlsson T, Tronci E, Kirik D, Björklund A, Carta M. Serotonin neuron-dependent and -independent reduction of dyskinesia by 5-HT1A and 5-HT1B receptor agonists in the rat Parkinson model. Exp Neurol 2009;219:298-307.
109. Tashiro Y, Kaneko T, Sugimoto T, Nagatsu I, Kikuchi H, Mizuno N. Striatal neurons with aromatic L-amino acid decarboxylase-like immunoreactivity in the rat. Neurosci Lett 1989;100:29-34.
110. Mura A, Jackson D, Manley MS, Young SJ, Groves PM. Aromatic L-amino acid decarboxylase immunoreactive cells in the rat striatum: a possible site for the conversion of exogenous L-DOPA to dopamine. Brain Res 1995;704:51-60.
111. Lopez-Real A, Rodriguez-Pallares J, Guerra MJ, Labandeira-Garcia JL. Localization and functional significance of striatal neurons immunoreactive to aromatic L-amino acid decarboxylase or tyrosine hydroxylase in rat Parkinsonian models. Brain Res 2003;969:135-146.
112. Nakamura K, Ahmed M, Barr E, Leiden JM, Kang UJ. The localization and functional contribution of striatal aromatic L-amino acid decarboxylase to L-3, 4-dihydroxyphenylalanine decarboxylation in rodent parkinsonian models. Cell Transplant 2000;9:567-576.
113. Kang UJ, Park DH, Wessel T, Baker H, Joh TH. Dopa-decarboxylation in the striata of rats with unilateral substantia nigra lesions. Neurosci Lett 1992;147:53-57.
114. Togasaki DM, Tan L, Protell P, Di Monte DA, Quik M, Langston JW. Levodopa induces dyskinesias in normal squirrel monkeys. Ann Neurol 2001;50:254-257.