Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson's disease

Neurobiology of Disease

Volumn 73, Issue , 2015, Pages 377-387

  Bortolanza, Mariza ^a   Cavalcanti Kiwiatkoski, Roberta ^a   Padovan Neto, Fernando E ^a   da Silva, Célia Aparecida ^a   Mitkovski, Miso ^c   Raisman Vozari, Rita ^b   Del Bel, Elaine ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b INSTITUT DU CERVEAU ET DE LA MOELLE ÉPINIÈRE   (France)

^c MAX PLANCK INSTITUTE OF EXPERIMENTAL MEDICINE   (Germany)

Author keywords

6 OHDA lesion; GFAP; Glial cells; INOS; Neuroinflammation; OX 42

Indexed keywords

7 NITROINDAZOLE; BENSERAZIDE; CD11B ANTIGEN; GLIAL FIBRILLARY ACIDIC PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; LEVODOPA; MACROGOL; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE INHIBITOR; OXIDOPAMINE; SODIUM CHLORIDE; 7-NITROINDAZOLE; ANTIPARKINSON AGENT; INDAZOLE DERIVATIVE; NEUROPROTECTIVE AGENT; NITRIC OXIDE SYNTHASE;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; CELL COUNT; CELL STRUCTURE; CONTROLLED STUDY; CORPUS STRIATUM; DRUG EFFECT; DYSKINESIA; GLIA CELL; GLOBUS PALLIDUS; IMMUNOREACTIVITY; MALE; MEDIAL FOREBRAIN BUNDLE; MICROGLIA; NERVE CELL STIMULATION; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PARKINSON DISEASE; PROTEIN EXPRESSION; RAT; TREATMENT DURATION; UPREGULATION; WISTAR RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; DISEASE MODEL; DYSKINESIA, DRUG-INDUCED; GLIA; INFLAMMATION; METABOLISM;

ANIMALS; ANTIPARKINSON AGENTS; DISEASE MODELS, ANIMAL; DYSKINESIA, DRUG-INDUCED; INDAZOLES; INFLAMMATION; LEVODOPA; MALE; NEUROGLIA; NEUROPROTECTIVE AGENTS; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PARKINSON DISEASE; RATS; RATS, WISTAR; UP-REGULATION;

EID: 84909580553     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2014.10.017     Document Type: Article

References (122)

1. Agid Y., et al. Adverse reactions to levodopa: drug toxicity or progression of disease?. Lancet 1998, 351:851-852.
2. Andersson M., et al. Striatal fosB expression is causally linked with l-DOPA-induced abnormal involuntary movements and the associated upregulation of striatal prodynorphin mRNA in a rat model of Parkinson's disease. Neurobiol. Dis. 1999, 6:461-474.
3. Attwell D., et al. Glial and neuronal control of brain blood flow. Nature 2010, 468:232-243.
4. Banati R.B., et al. Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease. Mov. Disord. 1998, 13:221-227.
5. Barcia C., et al. Persistent phagocytic characteristics of microglia in the substantia nigra of long-term Parkinsonian macaques. J. Neuroimmunol. 2013, 261:60-66.
6. Barnum C.J., et al. Exogenous corticosterone reduces l-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta. Neuroscience 2008, 156:30-41.
7. Bartels A.L., Leenders K.L. Neuroinflammation in the pathophysiology of Parkinson's disease: evidence from animal models to human in vivo studies with [11C]-PK11195 PET. Mov. Disord. 2007, 22:1852-1856.
8. Becker C., et al. NSAID use and risk of Parkinson disease: a population-based case-control study. Eur. J. Neurol. 2011, 18:1336-1342.
9. Blandini F. Neural and immune mechanisms in the pathogenesis of Parkinson's disease. J. Neuroimmune Pharmacol. 2013, 8:189-201.
10. Bland-Ward P.A., Moore P.K. 7-Nitro indazole derivatives are potent inhibitors of brain, endothelium and inducible isoforms of nitric oxide synthase. Life Sci. 1995, 57:L131-L135.
11. Boka G., et al. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci. Lett. 1994, 172:151-154.
12. Braak H., et al. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol. Aging 2003, 24:197-211.
13. Buck K., Ferger B. Intrastriatal inhibition of aromatic amino acid decarboxylase prevents l-DOPA-induced dyskinesia: a bilateral reverse in vivo microdialysis study in 6-hydroxydopamine lesioned rats. Neurobiol. Dis. 2008, 29:210-220.
14. Carta M., et al. Role of striatal l-DOPA in the production of dyskinesia in 6-hydroxydopamine lesioned rats. J. Neurochem. 2006, 96:1718-1727.
15. Cenci M.A. Dopamine dysregulation of movement control in l-DOPA-induced dyskinesia. Trends Neurosci. 2007, 30:236-243.
16. Cenci M.A., Lindgren H.S. Advances in understanding l-DOPA-induced dyskinesia. Curr. Opin. Neurobiol. 2007, 17:665-671.
17. Cenci M.A., et al. l-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA. Eur. J. Neurosci. 1998, 10:2694-2706.
18. Cenci M.A., et al. Changes in the regional and compartmental distribution of FosB- and JunB-like immunoreactivity induced in the dopamine-denervated rat striatum by acute or chronic l-dopa treatment. Neuroscience 1999, 94:515-527.
19. Chen H., et al. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann. Neurol. 2005, 58:963-967.
20. Coleman J.W. Nitric oxide in immunity and inflammation. Int. Immunopharmacol. 2001, 1:1397-1406.
21. Colton C.A. Heterogeneity of microglial activation in the innate immune response in the brain. J. Neuroimmune Pharmacol. 2009, 4:399-418.
22. Contestabile A., et al. Brain nitric oxide and its dual role in neurodegeneration/neuroprotection: understanding molecular mechanisms to devise drug approaches. Curr. Med. Chem. 2003, 10:2147-2174.
23. Cools A.R., et al. Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia. Neuroscience 1989, 33:535-542.
24. Crossman A.R. A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's disease: implications for future strategies in treatment. Mov. Disord. 1990, 5:100-108.
25. Cunningham C., et al. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J. Neurosci. 2005, 25:9275-9284.
26. Czarnecka A., et al. Alterations in the expression of nNOS in the substantia nigra and subthalamic nucleus of 6-OHDA-lesioned rats: the effects of chronic treatment with l-DOPA and the nitric oxide donor, molsidomine. Brain Res. 2013, 1541:92-105.
27. Dauer W., Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003, 39:889-909.
28. Del-Bel E., et al. Role of nitric oxide on motor behavior. Cell. Mol. Neurobiol. 2005, 25:371-392.
29. Del-Bel E., et al. Role of nitric oxide in motor control: implications for Parkinson's disease pathophysiology and treatment. Curr. Pharm. Des. 2011, 17:471-488.
30. Del-Bel E., et al. Counteraction by Nitric oxide synthase inhibitor of neurochemical alterations of dopaminergic system in 6-OHDA-lesioned rats under l-DOPA treatment. Neurotox. Res. 2014, 25:33-44.
31. DeLong M., Wichmann T. Deep brain stimulation for movement and other neurologic disorders. Ann. N. Y. Acad. Sci. 2012, 1265:1-8.
32. Doherty G.H. Nitric oxide in neurodegeneration: potential benefits of non-steroidal anti-inflammatories. Neurosci. Bull. 2011, 27:366-382.
33. Driver J.A., et al. Use of non-steroidal anti-inflammatory drugs and risk of Parkinson's disease: nested case-control study. BMJ 2011, 342:d198.
34. Duke D.C., et al. The medial and lateral substantia nigra in Parkinson's disease: mRNA profiles associated with higher brain tissue vulnerability. Neurogenetics 2007, 8:83-94.
35. Eve D.J., et al. Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson's disease. Brain Res. Mol. Brain Res. 1998, 63:62-71.
36. Fahn S. The history of dopamine and levodopa in the treatment of Parkinson's disease. Mov. Disord. 2008, 23(Suppl. 3):S497-S508.
37. Fasano S., et al. Inhibition of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) signaling in the striatum reverts motor symptoms associated with l-dopa-induced dyskinesia. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:21824-21829.
38. Ferrer I. Early involvement of the cerebral cortex in Parkinson's disease: convergence of multiple metabolic defects. Prog. Neurobiol. 2009, 88:89-103.
39. Ferrer I. Neuropathology and neurochemistry of nonmotor symptoms in Parkinson's disease. Park. Dis. 2011, 2011:708-404.
40. Ferrer I., et al. Neurochemistry and the non-motor aspects of PD. Neurobiol. Dis. 2012, 46:508-526.
41. Gao H.M., et al. Novel anti-inflammatory therapy for Parkinson's disease. Trends Pharmacol. Sci. 2003, 24:395-401.
42. Gatto E.M., et al. Overexpression of neutrophil neuronal nitric oxide synthase in Parkinson's disease. Nitric Oxide 2000, 4:534-539.
43. Gerhard A., et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol. Dis. 2006, 21:404-412.
44. Gomes M.Z., Del Bel E.A. Effects of electrolytic and 6-hydroxydopamine lesions of rat nigrostriatal pathway on nitric oxide synthase and nicotinamide adenine dinucleotide phosphate diaphorase. Brain Res. Bull. 2003, 62:107-115.
45. Gomes M.Z., et al. A nitric oxide synthase inhibitor decreases 6-hydroxydopamine effects on tyrosine hydroxylase and neuronal nitric oxide synthase in the rat nigrostriatal pathway. Brain Res. 2008, 1203:160-169.
46. Gomide V., et al. Dopamine cell morphology and glial cell hypertrophy and process branching in the nigrostriatal system after striatal 6-OHDA analyzed by specific sterological tools. Int. J. Neurosci. 2005, 115:557-582.
47. Guzik T.J., et al. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol. 2003, 54:469-487.
48. Handy R.L., Moore P.K. A comparison of the effects of l-NAME, 7-NI and l-NIL on carrageenan-induced hindpaw oedema and NOS activity. Br. J. Pharmacol. 1998, 123:1119-1126.
49. Henning J., et al. Differential astroglial activation in 6-hydroxydopamine models of Parkinson's disease. Neurosci Res. 2008, 62:246-253.
50. Henry V., et al. Kinetics of microglial activation and degeneration of dopamine-containing neurons in a rat model of Parkinson disease induced by 6-hydroxydopamine. J. Neuropathol. Exp. Neurol. 2009, 68:1092-1102.
51. Hirsch E.C., Hunot S. Neuroinflammation in Parkinson's disease: a target for neuroprotection?. Lancet Neurol. 2009, 8:382-397.
52. Hunot S., et al. Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience 1996, 72:355-363.
53. Hunot S., et al. Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:7531-7536.
54. Hurley M.J., et al. Proteomic analysis of striatum from MPTP-treated marmosets (Callithrix jacchus) with l-DOPA-induced dyskinesia of differing severity. J. Mol. Neurosci. 2014, 52:302-312.
55. Iravani M.M., Jenner P. Mechanisms underlying the onset and expression of levodopa-induced dyskinesia and their pharmacological manipulation. J. Neural Transm. 2011, 118:1661-1690.
56. Iravani M.M., et al. Striatal plasticity in Parkinson's disease and l-dopa induced dyskinesia. Parkinsonism Relat. Disord. 2012, 18(Suppl. 1):S123-S125.
57. Jenner P. Molecular mechanisms of l-DOPA-induced dyskinesia. Nat. Rev. Neurosci. 2008, 9:665-677.
58. Jenner P. Wearing off, dyskinesia, and the use of continuous drug delivery in Parkinson's disease. Neurol. Clin. 2013, 31:S17-S35.
59. Jenner P.G., Brin M.F. Levodopa neurotoxicity: experimental studies versus clinical relevance. Neurology 1998, 50:S39-S43. (discussion S44-8).
60. Kalisch B.E., et al. Differential action of 7-nitro indazole on rat brain nitric oxide synthase. Neurosci. Lett. 1996, 219:75-78.
61. Kim J.H., et al. Microglia-inhibiting activity of Parkinson's disease drug amantadine. Neurobiol. Aging 2012, 33:2145-2159.
62. Knott C., et al. Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol. Cell. Neurosci. 2000, 16:724-739.
63. Konradi C., et al. Transcriptome analysis in a rat model of l-DOPA-induced dyskinesia. Neurobiol. Dis. 2004, 17:219-236.
64. Langston J.W., et al. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol. 1999, 46:598-605.
65. L'Episcopo F., et al. Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J. Neuroinflammation 2010, 7:83.
66. Lindgren H.S., et al. The "motor complication syndrome" in rats with 6-OHDA lesions treated chronically with l-DOPA: relation to dose and route of administration. Behav. Brain Res. 2007, 177:150-159.
67. Lortet S., et al. Striatal molecular signature of subchronic subthalamic nucleus high frequency stimulation in parkinsonian rat. PLoS One 2013, 8:e60447.
68. Lundblad M., et al. Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease. Eur. J. Neurosci. 2002, 15:120-132.
69. Maia S., et al. Longitudinal and parallel monitoring of neuroinflammation and neurodegeneration in a 6-hydroxydopamine rat model of Parkinson's disease. Synapse 2012, 66:573-583.
70. Matsumura M., et al. Activity of pallidal neurons in the monkey during dyskinesia induced by injection of bicuculline in the external pallidum. Neuroscience 1995, 65:59-70.
71. Maurice N., et al. Position of the ventral pallidum in the rat prefrontal cortex-basal ganglia circuit. Neuroscience 1997, 80:523-534.
72. McGeer P.L., McGeer E.G. Glial reactions in Parkinson's disease. Mov. Disord. 2008, 23:474-483.
73. McGeer P.L., et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 1988, 38:1285-1291.
74. Meissner W., 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.
75. Meurers B.H., et al. Dopamine depletion induces distinct compensatory gene expression changes in DARPP-32 signal transduction cascades of striatonigral and striatopallidal neurons. J Neurosci. 2009, 29:6828-6839.
76. Mirza B., et al. The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease. Neuroscience 2000, 95:425-432.
77. Mogi M., et al. Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci. Lett. 1994, 180:147-150.
78. Mogi M., et al. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci. Lett. 1994, 165:208-210.
79. Mogi M., et al. Transforming growth factor-beta 1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease. Neurosci Lett. 1995, 193:129-132.
80. Mogi M., et al. p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain. Neurosci. Lett. 2007, 414:94-97.
81. Moore S., Thanos S. The concept of microglia in relation to central nervous system disease and regeneration. Prog. Neurobiol. 1996, 48:441-460.
82. Moore P.K., et al. 7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure. Br. J. Pharmacol. 1993, 108:296-297.
83. Moore D.J., et al. Molecular pathophysiology of Parkinson's disease. Annu. Rev. Neurosci. 2005, 28:57-87.
84. Murer M.G., et al. Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions. Ann. Neurol. 1998, 43:561-575.
85. Nayak D., et al. Microglia development and function. Annu. Rev. Immunol. 2014, 32:367-402.
86. Nedergaard M., et al. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 2003, 26:523-530.
87. Niranjan R. The role of inflammatory and oxidative stress mechanisms in the pathogenesis of Parkinson's disease: focus on astrocytes. Mol. Neurobiol. 2014, 49:28-38.
88. Novaretti N., et al. Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats. Braz. J. Med. Biol. Res. 2010, 43:1047-1053.
89. Obeso J.A., et al. Functional organization of the basal ganglia: therapeutic implications for Parkinson's disease. Mov. Disord. 2008, 23(Suppl. 3):S548-S559.
90. Ohlin K.E., et al. Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia. Brain 2011, 134:2339-2357.
91. Ohlin K.E., et al. Impact of l-DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease. Neuroimage 2012, 61:228-239.
92. Olanow C.W., et al. Levodopa therapy for Parkinson's disease: challenges and future prospects. Mov. Disord. 2008, 23(Suppl. 3):S495-S496.
93. Ouchi Y., et al. Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann. Neurol. 2005, 57:168-175.
94. Padovan-Neto F.E., et al. Nitric oxide synthase inhibition attenuates l-DOPA-induced dyskinesias in a rodent model of Parkinson's disease. Neuroscience 2009, 159:927-935.
95. Padovan-Neto F.E., et al. Nitric oxide synthase inhibitor improves de novo and long-term l-DOPA-induced dyskinesia in hemiparkinsonian rats. Front. Syst. Neurosci. 2011, 5:40.
96. Padovan-Neto F.E., et al. Anti-dyskinetic effect of the neuronal nitric oxide synthase inhibitor is linked to decrease of FosB/deltaFosB expression. Neurosci. Lett. 2013, 541:126-131.
97. Padovan-Neto F.E., et al. Effects of prolonged neuronal nitric oxide synthase inhibition on the development and expression of l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats. Neuropharmacol 2014, 89C:87-99.
98. Paxinos G., Watson C. The rat brain in stereotaxic coordinates 2007, Academic Press, San Diego.
99. Picconi B., et al. Striatal metabotropic glutamate receptor function following experimental parkinsonism and chronic levodopa treatment. Brain 2002, 125:2635-2645.
100. Pradhan S., Andreasson K. Commentary: progressive inflammation as a contributing factor to early development of Parkinson's disease. Exp. Neurol. 2013, 241:148-155.
101. Przedborski S. Inflammation and Parkinson's disease pathogenesis. Mov. Disord. 2010, 25(Suppl. 1):S55-S57.
102. Qureshi G.A., et al. Increased cerebrospinal fluid concentration of nitrite in Parkinson's disease. Neuroreport 1995, 6:1642-1644.
103. Ransohoff R.M., Perry V.H. Microglial physiology: unique stimuli, specialized responses. Annu. Rev. Immunol. 2009, 27:119-145.
104. Robelet S., et al. Chronic l-DOPA treatment increases extracellular glutamate levels and GLT1 expression in the basal ganglia in a rat model of Parkinson's disease. Eur. J. Neurosci. 2004, 20:1255-1266.
105. Schulz J.B., et al. The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases. Mol. Cell. Biochem. 1997, 174:193-197.
106. Shimoji M., et al. CXCR4 and CXCL12 expression is increased in the nigro-striatal system of Parkinson's disease. Neurotox. Res. 2009, 16:318-328.
107. Sofroniew M.V. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009, 32:638-647.
108. Sofroniew M.V., Vinters H.V. Astrocytes: biology and pathology. Acta Neuropathol. 2010, 119:7-35.
109. Southan G.J., Szabó C. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem. Pharmacol. 1996, 51:383-394.
110. Spooren W.P., et al. Dopamine D1 receptors in the sub-commissural part of the globus pallidus and their role in oro-facial dyskinesia in cats. Eur. J. Pharmacol. 1991, 204:217-222.
111. Strutt A.M., et al. Five-year follow-up of unilateral posteroventral pallidotomy in Parkinson's disease. Surg. Neurol. 2009, 71:551-558.
112. Sun D., Jakobs T.C. Structural remodeling of astrocytes in the injured CNS. Neuroscientist 2012, 18:567-588.
113. Takuma K., et al. Neuronal nitric oxide synthase inhibition attenuates the development of l-DOPA-induced dyskinesia in hemi-Parkinsonian rats. Eur. J. Pharmacol. 2012, 683:166-173.
114. Tansey M.G., Goldberg M.S. Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol. Dis. 2010, 37:510-518.
115. Teismann P., et al. Pathogenic role of glial cells in Parkinson's disease. Mov. Disord. 2003, 18:121-129.
116. Tomasiuk R., et al. Ropinirole treatment in Parkinson's disease associated with higher serum level of inflammatory biomarker NT-proCNP. Neurosci. Lett. 2014, 566C:147-150.
117. Tripathi P., et al. The role of nitric oxide in inflammatory reactions. FEMS Immunol. Med. Microbiol. 2007, 51:443-452.
118. Turner M.S., et al. Alterations in responses of ventral pallidal neurons to excitatory amino acids after long-term dopamine depletion. J. Pharmacol. Exp. Ther. 2002, 301:371-381.
119. Wang Y., et al. Genome-wide microarray analysis identifies a potential role for striatal retrograde endocannabinoid signaling in the pathogenesis of experimental l-DOPA-induced dyskinesia. Synapse. 2014, 68:332-343.
120. Westin J.E., et al. Endothelial proliferation and increased blood-brain barrier permeability in the basal ganglia in a rat model of 3,4-dihydroxyphenyl-l-alanine-induced dyskinesia. J. Neurosci. 2006, 26:9448-9461.
121. Westin J.E., et al. Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of l-DOPA-induced dyskinesia and the role of dopamine D1 receptors. Biol. Psychiatry 2007, 62:800-810.
122. Winkler C., et al. l-DOPA-induced dyskinesia in the intrastriatal 6-hydroxydopamine model of Parkinson's disease: relation to motor and cellular parameters of nigrostriatal function. Neurobiol. Dis. 2002, 10:165-186.