Prospects for cannabinoid therapies in basal ganglia disorders

British Journal of Pharmacology

Volumn 163, Issue 7, 2011, Pages 1365-1378

  Fernández Ruiz, Javier ^a,b,c   Moreno Martet, Miguel ^a,b,c   Rodríguez Cueto, Carmen ^a,b,c   Palomo Garo, Cristina ^a,b,c   Gõmez Cañas, María ^a,b,c   Valdeolivas, Sara ^a,b,c   Guaza, Carmen ^d   Romero, Julián ^b,e   Guzmán, Manuel ^a,b,c   Mechoulam, Raphael ^f   Ramos, José A ^a,b,c  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED SOBRE ENFERMEDADES NEURODEGENERATIVAS CIBERNED   (Spain)

^c INSTITUTO RAMÓN Y CAJAL DE INVESTIGACIÓN SANITARIA IRYCIS   (Spain)

^d INSTITUTO CAJAL   (Spain)

^e HOSPITAL UNIVERSITARIO FUNDACIÓN ALCORCÓN   (Spain)

^f HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

basal ganglia; cannabinoid signalling system; cannabinoids; CB 1 receptors; CB 2 receptors; Huntington's disease; neurodegeneration; neuroprotection; Parkinson's disease

Indexed keywords

4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; 4 [4 (1,1 DIMETHYLHEPTYL) 2,6 DIMETHOXYPHENYL] 6,6 DIMETHYLBICYCLO[3.1.1]HEPT 2 EN 2 YLMETHANOL; ACETYLCYSTEINE; ALPHA TOCOPHEROL; ASCORBIC ACID; CANNABIDIOL; CANNABINOID; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR AGONIST; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; CANNABINOID 2 RECEPTOR AGONIST; CANNABINOID DERIVATIVE; CANNABINOL; CANNABIS; DEXANABINOL; DRONABINOL; GINSENG EXTRACT; KAEMPFEROL; LEVONANTRADOL; MELATONIN; NABILONE; PRASTERONE; S ALLYLCYSTEINE; TAURINE; TETRAHYDROCANNABIVARIN; UBIDECARENONE; UNCLASSIFIED DRUG; ANTIOXIDANT; DELTA8 TETRAHYDROCANNABINOL; N (4 HYDROXYPHENYL)ARACHIDONAMIDE; NABIXIMOLS; REACTIVE OXYGEN METABOLITE; VANILLOID RECEPTOR 1;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ASTROCYTE; BRAIN CORTEX; CORPUS STRIATUM; DISEASE COURSE; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG STRUCTURE; DYSKINESIA; DYSTONIA; EXCITOTOXICITY; EXTRAPYRAMIDAL SYNDROME; GILLES DE LA TOURETTE SYNDROME; GLOBUS PALLIDUS; HUMAN; HUNTINGTON CHOREA; HYPERKINESIA; INFLAMMATION; MICROGLIA; NERVE CELL LESION; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SUBTHALAMIC NUCLEUS; TIC; UPREGULATION; CELL PROTECTION; DRUG EFFECT; DRUG TARGETING; NERVE INJURY; NEUROPATHOLOGY; PROTEIN FUNCTION;

ANIMALS; BASAL GANGLIA; BASAL GANGLIA DISEASES; CANNABINOIDS; HUMANS; RECEPTOR, CANNABINOID, CB2;

EID: 79960317325     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01365.x     Document Type: Review

References (114)

1. Alkaitis MS, Solorzano C, Landry RP, Piomelli D, DeLeo JA, Romero-Sandoval EA, (2010). Evidence for a role of endocannabinoids, astrocytes and p38 phosphorylation in the resolution of postoperative pain. PLoS ONE 5: e10891.
2. Amor S, Puentes F, Baker D, van der Valk P, (2010). Inflammation in neurodegenerative diseases. Immunology 129: 154-169.
3. Ashton JC, Rahman RM, Nair SM, Sutherland BA, Glass M, Appleton I, (2007). Cerebral hypoxia-ischemia and middle cerebral artery occlusion induce expression of the cannabinoid CB2 receptor in the brain. Neurosci Lett 412: 114-117. (Pubitemid 46074356)
4. Bahr BA, Karanian DA, Makanji SS, Makriyannis A, (2006). Targeting the endocannabinoid system in treating brain disorders. Expert Opin Investig Drugs 15: 351-365.
5. Battista N, Bari M, Tarditi A, Mariotti C, Bachoud-Lévi AC, Zuccato C, et al,. (2007). Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's disease mutation in peripheral lymphocytes. Neurobiol Dis 27: 108-116. (Pubitemid 46924866)
6. Beltramo M, Bernardini N, Bertorelli R, Campanella M, Nicolussi E, Fredduzzi S, et al,. (2006). CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. Eur J Neurosci 23: 1530-1538.
7. Benito C, Nuñez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ, et al,. (2003). Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. J Neurosci 23: 11136-11141. (Pubitemid 37548949)
8. Benito C, Kim WK, Chavarría I, Hillard CJ, Mackie K, Tolõn RM, et al,. (2005). A glial endogenous cannabinoid system is upregulated in the brains of macaques with simian immunodeficiency virus-induced encephalitis. J Neurosci 25: 2530-2536. (Pubitemid 40365164)
9. Benito C, Romero JP, Tolon RM, Clemente D, Docagne F, Hillard CJ, et al,. (2007). Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. J Neurosci 27: 2396-2402. (Pubitemid 46340977)
10. Benito C, Tolõn RM, Pazos MR, Núñez E, Castillo AI, Romero J, (2008). Cannabinoid CB2 receptors in human brain inflammation. Br J Pharmacol 153: 277-285.
11. Blázquez C, Chiarlone A, Sagredo O, Aguado T, Pazos MR, Resel E, et al,. (2011). Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease. Brain 134: 119-136.
12. Borrell-Pages M, Zala D, Humbert S, Saudou F, (2006). Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies. Cell Mol Life Sci 63: 2642-2660. (Pubitemid 44800717)
13. Brouillet E, Jacquard C, Bizat N, Blum D, (2005). 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease. J Neurochem 95: 1521-1540. (Pubitemid 41804051)
14. Calkins MJ, Jakel RJ, Johnson DA, Chan K, Kan YW, Johnson JA, (2005). Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci U S A 102: 244-249. (Pubitemid 40094460)
15. Calkins MJ, Townsend JA, Johnson DA, Johnson JA, (2010). Cystamine protects from 3-nitropropionic acid lesioning via induction of nf-e2 related factor 2 mediated transcription. Exp Neurol 224: 307-317.
16. Carroll CB, Bain PG, Teare L, Liu X, Joint C, Wroath C, et al,. (2004). Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology 63: 1245-1250. (Pubitemid 39350025)
17. Chen Y, Buck J, (2000). Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism. J Pharmacol Exp Ther 293: 807-812. (Pubitemid 30417845)
18. Chevaleyre V, Takahashi KA, Castillo PE, (2006). Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29: 37-76. (Pubitemid 44476839)
19. Consroe P, (1998). Brain cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol Dis 5: 534-551. (Pubitemid 29075849)
20. Correa F, Hernangõmez M, Mestre L, Loría F, Spagnolo A, Docagne F, et al,. (2010). Anandamide enhances IL-10 production in activated microglia by targeting CB2 receptors: roles of ERK1/2, JNK, and NF-kappaB. Glia 58: 135-147.
21. Curtis A, Rickards H, (2006). Nabilone could treat chorea and irritability in Huntington's disease. J Neuropsychiatry Clin Neurosci 18: 553-554. (Pubitemid 44713898)
22. Curtis A, Mitchell I, Patel S, Ives N, Rickards H, (2009). A pilot study using nabilone for symptomatic treatment in Huntington's disease. Mov Disord 24: 2254-2259.
23. Denovan-Wright EM, Robertson HA, (2000). Cannabinoid receptor messenger RNA levels decrease in subset neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington's disease mice. Neuroscience 98: 705-713. (Pubitemid 30417587)
24. Di Marzo V, (2008). Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 7: 438-455. (Pubitemid 351649182)
25. Di Marzo V, (2009). The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacol Res 60: 77-84.
26. Dowie MJ, Bradshaw HB, Howard ML, Nicholson LF, Faull RL, Hannan AJ, et al,. (2009). Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington's disease. Neuroscience 163: 456-465.
27. Eshhar N, Striem S, Kohen R, Tirosh O, Biegon A, (1995). Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist. Eur J Pharmacol 283: 19-29.
28. Esposito G, Scuderi C, Savani C, Steardo L Jr, De Filippis D, Cottone P, et al,. (2007). Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br J Pharmacol 151: 1272-1279. (Pubitemid 47255904)
29. Fabbrini G, Brotchie JM, Grandas F, Nomoto M, Goetz CG, (2007). Levodopa-induced dyskinesias. Mov Disord 22: 1379-1389. (Pubitemid 47280623)
30. Fernández-Espejo E, Caraballo I, Rodríguez de Fonseca F, El Banoua F, Ferrer B, Flores JA, et al,. (2005). Cannabinoid CB1 antagonists possess antiparkinsonian efficacy only in rats with very severe nigral lesion in experimental parkinsonism. Neurobiol Dis 18: 591-601. (Pubitemid 40332717)
31. Fernández-Ruiz J, (2009). The endocannabinoid system as a target for the treatment of motor dysfunction. Br J Pharmacol 156: 1029-1040.
32. Fernández-Ruiz J, González S, (2005). Cannabinoid control of motor function at the basal ganglia. In:, Pertwee RG, (ed.). Handbook of Experimental Pharmacology-168-Cannabinoids. Springer-Verlag: Heidelberg, pp. 479-507.
33. Fernández-Ruiz J, González S, Romero J, Ramos JA, (2005). Cannabinoids in neurodegeneration and neuroprotection. In:, Mechoulam R, (ed.). Cannabinoids As Therapeutics (MDT. Birkhaüser Verlag: Basel, Switzerland, pp. 79-109.
34. Fernández-Ruiz J, Romero J, Velasco G, Tolõn RM, Ramos JA, Guzmán M, (2007). Cannabinoid CB2 receptor: a new target for controlling neural cell survival? Trends Pharmacol Sci 28: 39-45. (Pubitemid 46038536)
35. Fernández-Ruiz J, García C, Sagredo O, Gõmez-Ruiz M, de Lago E, (2010). The endocannabinoid system as a target for the treatment of neuronal damage. Expert Opin Ther Targets 14: 387-404.
36. Ferrer I, Martinez A, Blanco R, Dalfõ E, Carmona M, (2010). Neuropathology of sporadic Parkinson's disease before the appearance of parkinsonism: preclinical Parkinson's disease. J Neural Transm (in press). doi: 10.1007/s00702-010-0482-8
37. Fontaine MA, Geddes JW, Banks A, Butterfield DA, (2000). Effect of exogenous and endogenous antioxidants on 3-nitropionic acid-induced in vivo oxidative stress and striatal lesions: insights into Huntington's disease. J Neurochem 75: 1709-1715.
38. 9-THCV in animal models of Parkinson's disease. Br J Pharmacol 163: 1495-1506.
39. García-Arencibia M, González S, de Lago E, Ramos JA, Mechoulam R, Fernández-Ruiz J, (2007). Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res 1134: 162-170. (Pubitemid 46135535)
40. García-Arencibia M, García C, Kurz A, Rodríguez- Navarro JA, Gispert-Sáchez S, Mena MA, et al,. (2009a). Cannabinoid CB1 receptors are early downregulated followed by a further upregulation in the basal ganglia of mice with deletion of specific park genes. J Neural Transm Suppl 73: 269-275.
41. García-Arencibia M, García C, Fernández-Ruiz J, (2009b). Cannabinoids and Parkinson's disease. CNS Neurol Disord Drug Targets 8: 432-439.
42. Gerdeman GL, Fernández-Ruiz J, (2008). The endocannabinoid system in the physiology and pathophysiology of the basal ganglia. In:, Kofalvi A, (ed.). Cannabinoids and the Brain. Springer-Verlag: Heidelberg, Germany, pp. 423-483.
43. Glass M, Dragunow M, Faull RLM, (2000). The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABA-A receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 97: 505-519. (Pubitemid 30320757)
44. González S, Scorticati C, García-Arencibia M, de Miguel R, Ramos JA, Fernández-Ruiz J, (2006). Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat model of Parkinson's disease. Brain Res 1073-1074: 209-219.
45. Grünblatt E, Zander N, Bartl J, Jie L, Monoranu CM, Arzberger T, et al,. (2007). Comparison analysis of gene expression patterns between sporadic Alzheimer's and Parkinson's disease. J Alzheimers Dis 12: 291-311.
46. Guzmán M, Sánchez C, (1999). Effects of cannabinoids on energy metabolism. Life Sci 65: 657-664. (Pubitemid 29362771)
47. 9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A 95: 8268-8273. (Pubitemid 28326102)
48. Heneka MT, Rodríguez JJ, Verkhratsky A, (2010). Neuroglia in neurodegeneration. Brain Res Rev 63: 189-211.
49. Herrera-Mundo MN, Silva-Adaya D, Maldonado PD, Galvan-Arzate S, Andres-Martinez L, Perez-De La Cruz V, et al,. (2006). S-Allylcysteine prevents the rat from 3-nitropropionic acid-induced hyperactivity, early markers of oxidative stress and mitochondrial dysfunction. Neurosci Res 56: 39-44. (Pubitemid 44292883)
50. Hurley MJ, Mash DC, Jenner P, (2003). Expression of cannabinoid CB1 receptor mRNA in basal ganglia of normal and parkinsonian human brain. J Neural Transm 110: 1279-1288. (Pubitemid 37500749)
51. Janero DR, Makriyannis A, (2009). Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis. Expert Opin Emerg Drugs 14: 43-65.
52. Jiménez-Del-Rio M, Daza-Restrepo A, Velez-Pardo C, (2008). The cannabinoid CP55,940 prolongs survival and improves locomotor activity in Drosophila melanogaster against paraquat: implications in Parkinson's disease. Neurosci Res 61: 404-411.
53. Kalonia H, Kumar P, Kumar A, (2010). Targeting oxidative stress attenuates malonic acid induced Huntington like behavioral and mitochondrial alterations in rats. Eur J Pharmacol 634: 46-52.
54. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M, (2009). Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89: 309-380.
55. Kelsey JE, Harris O, Cassin J, (2009). The CB1 antagonist rimonabant is adjunctively therapeutic as well as monotherapeutic in an animal model of Parkinson's disease. Behav Brain Res 203: 304-307.
56. Lagoa R, Lõpez-Sánchez C, Samhan-Arias AK, Gañan CM, Garcia-Martinez V, Gutierrez-Merino C, (2009). Kaempferol protects against rat striatal degeneration induced by 3-nitropropionic acid. J Neurochem 111: 473-487.
57. Lanciego JL, Barroso-Chinea P, Rico AJ, Conte-Perales L, Callén L, Roda E, et al,. (2011). Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of Macaca fascicularis. J Psychopharmacol 25: 97-104.
58. 1 receptors in the basal ganglia of a transgenic model of Huntington's disease. Brain Res 929: 236-242. (Pubitemid 34178339)
59. 1 receptors and alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington's disease. Synapse 44: 23-35. (Pubitemid 34174375)
60. Lastres-Becker I, de Miguel R, De Petrocellis L, Makriyannis A, Di Marzo V, Fernández-Ruiz J, (2003). Compounds acting at the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington's disease. J Neurochem 84: 1097-1109. (Pubitemid 36330662)
61. Lastres-Becker I, Bizat N, Boyer F, Hantraye P, Fernández-Ruiz JJ, Brouillet E, (2004). Potential involvement of cannabinoid receptors in 3-nitropropionic acid toxicity in vivo: implication for Huntington's disease. Neuroreport 15: 2375-2379. (Pubitemid 39488923)
62. Lastres-Becker I, Molina-Holgado F, Ramos JA, Mechoulam R, Fernández-Ruiz J, (2005). Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease. Neurobiol Dis 19: 96-107. (Pubitemid 40544727)
63. Lee JK, Tran T, Tansey MG, (2009). Neuroinflammation in Parkinson's disease. J Neuroimmune Pharmacol 4: 419-429.
64. Loría F, Petrosino S, Mestre L, Spagnolo A, Correa F, Hernangõmez M, et al,. (2008). Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci 28: 633-641.
65. Lull ME, Block ML, (2010). Microglial activation and chronic neurodegeneration. Neurotherapeutics 7: 354-365.
66. Luongo L, Palazzo E, Tambaro S, Giordano C, Gatta L, Scafuro MA, et al,. (2009). 1-(2′,4′-dichlorophenyl)-6-methyl-N-cyclohexylamine-1,4- dihydroindeno[1,2-c]pyrazole-3-carboxamide, a novel CB2 agonist, alleviates neuropathic pain through functional microglial changes in mice. Neurobiol Dis 37: 177-185.
67. Maccarrone M, Battista N, Centonze D, (2007). The endocannabinoid pathway in Huntington's disease: a comparison with other neurodegenerative diseases. Prog Neurobiol 81: 349-379. (Pubitemid 46528640)
68. Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN, (2005). Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 95: 437-445. (Pubitemid 41457512)
69. Marsicano G, Lutz B, (2006). Neuromodulatory functions of the endocannabinoid system. J Endocrinol Invest 29: 27-46.
70. 1. J Neurochem 80: 448-456. (Pubitemid 36383028)
71. Martínez-Orgado J, Fernández-Ruiz J, Romero J, (2009). The endocannabinoid system in neuropathological states. Int Rev Psychiatry 21: 172-180.
72. Mesnage V, Houeto JL, Bonnet AM, Clavier I, Arnulf I, Cattelin F, et al,. (2004). Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease. Clin Neuropharmacol 27: 108-110. (Pubitemid 38746008)
73. Molina-Holgado F, Pinteaux E, Moore JD, Molina-Holgado E, Guaza C, Gibson RM, et al,. (2003). Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. J Neurosci 23: 6470-6474. (Pubitemid 36909872)
74. Mukhopadhyay S, Das S, Williams EA, Moore D, Jones JD, Zahm DS, et al,. (2006). Lipopolysaccharide and cyclic AMP regulation of CB2 cannabinoid receptor levels in rat brain and mouse RAW 264.7 macrophages. J Neuroimmunol 181: 82-92. (Pubitemid 44827292)
75. Müller-Vahl KR, (2009). Tourette's syndrome. Curr Top Behav Neurosci 1: 397-410.
76. Müller-Vahl KR, Schneider U, Emrich HM, (1999). Nabilone increases choreatic movements in Huntington's disease. Mov Disord 14: 1038-1040.
77. Nagatsu T, Sawada M, (2007). Biochemistry of postmortem brains in Parkinson's disease: historical overview and future prospects. J Neural Transm Suppl 72: 113-120.
78. Nam E, Lee SM, Koh SE, Joo WS, Maeng S, Im HI, et al,. (2005). Melatonin protects against neuronal damage induced by 3-nitropropionic acid in rat striatum. Brain Res 1046: 90-96. (Pubitemid 40775877)
79. Núñez E, Benito C, Tolõn RM, Hillard CJ, Griffin WS, Romero J, (2008). Glial expression of cannabinoid CB2 receptors and fatty acid amide hydrolase are beta amyloid-linked events in Down's syndrome. Neuroscience 151: 104-110.
80. Palazuelos J, Davoust N, Julien B, Hatterer E, Aguado T, Mechoulam R, et al,. (2008). The CB2 cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis. J Biol Chem 283: 13320-13329.
81. Palazuelos J, Aguado T, Pazos MR, Julien B, Carrasco C, Resel E, et al,. (2009). Microglial CB2 cannabinoid receptors are neuroprotective in Huntington's disease excitotoxicity. Brain 132: 3152-3164.
82. Pazos MR, Sagredo O, Fernández-Ruiz J, (2008). The endocannabinoid system in Huntington's disease. Curr Pharm Des 14: 2317-2325.
83. Pérez-Rial S, García-Gutiérrez MS, Molina JA, Pérez-Nievas BG, Ledent C, Leiva C, et al,. (2011). Increased vulnerability to 6-hydroxydopamine lesion and reduced development of dyskinesias in mice lacking CB1 cannabinoid receptors. Neurobiol Aging 32: 631-645.
84. Pertwee RG, (2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 156: 397-411.
85. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, et al,. (2010). International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 62: 588-631.
86. Pintor A, Tebano MT, Martire A, Grieco R, Galluzzo M, Scattoni ML, et al,. (2006). The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum. Neuropharmacology 51: 1004-1012. (Pubitemid 44528606)
87. Price DA, Martinez AA, Seillier A, Koek W, Acosta Y, Fernández E, et al,. (2009). WIN55,212-2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Eur J Neurosci 29: 2177-2186.
88. Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML, (2005). Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 25: 1904-1913. (Pubitemid 40289395)
89. Romero-Sandoval A, Nutile-McMenemy N, DeLeo JA, (2008). Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury. Anesthesiology 108: 722-734. (Pubitemid 351440594)
90. Roze E, Bonnet C, Betuing S, Caboche J, (2010). Huntington's disease. Adv Exp Med Biol 685: 45-63.
91. Sagredo O, Ramos JA, Decio A, Mechoulam R, Fernández-Ruiz J, (2007). Cannabidiol reduced the striatal atrophy caused 3-nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV1 and adenosine A2A receptors. Eur J Neurosci 26: 843-851. (Pubitemid 47274613)
92. Sagredo O, González S, Aroyo I, Pazos MR, Benito C, Lastres-Becker I, et al,. (2009). Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington's disease. Glia 57: 1154-1167.
93. Sagredo O, Pazos MR, Satta V, Ramos JA, Pertwee RG, Fernández-Ruiz J, (2011). Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease. J. Neurosci Res (in press).
94. Sañudo-Peña MC, Walker JM, (1997). Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat. J Neurophysiol 77: 1635-1638. (Pubitemid 27137055)
95. Scotter EL, Goodfellow CE, Graham ES, Dragunow M, Glass M, (2010). Neuroprotective potential of CB1 receptor agonists in an in vitro model of Huntington's disease. Br J Pharmacol 160: 747-761.
96. Sieradzan KA, Fox SH, Hill M, Dick JP, Crossman AR, Brotchie JM, (2001). Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study. Neurology 57: 2108-2111. (Pubitemid 33126882)
97. Smith SR, Terminelli C, Denhardt G, (2000). Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice. J Pharmacol Exp Ther 293: 136-150. (Pubitemid 30180933)
98. Stella N, (2009). Endocannabinoid signaling in microglial cells. Neuropharmacology 56 (Suppl. 1): 244-253.
99. Tadros MG, Khalifa AE, Abdel-Naim AB, Arafa HM, (2005). Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington's disease phenotype. Pharmacol Biochem Behav 82: 574-582. (Pubitemid 41827601)
100. Thomas B, Beal MF, (2007). Parkinson's disease. Hum Mol Genet 16: R183-R194.
101. Torres E, Gutierrez-Lopez MD, Borcel E, Peraile I, Mayado A, O'Shea E, et al,. (2010). Evidence that MDMA ('ecstasy') increases cannabinoid CB2 receptor expression in microglial cells: role in the neuroinflammatory response in rat brain. J Neurochem 113: 67-78.
102. Túnez I, Muñoz MC, Montilla P, (2005). Treatment with dehydroepiandrosterone prevents oxidative stress induced by 3-nitropropionic acid in synaptosomes. Pharmacology 74: 113-118. (Pubitemid 40981096)
103. Van Laere K, Casteels C, Dhollander I, Goffin K, Grachev I, Bormans G, et al,. (2010). Widespread decrease of type 1 cannabinoid receptor availability in Huntington disease in vivo. J Nucl Med 51: 1413-1417.
104. Veldhuis WB, van der Stelt M, Wadman MW, van Zadelhoff G, Maccarrone M, Fezza F, et al,. (2003). Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxicity in the rat: role of vanilloid receptors and lipoxygenases. J Neurosci 23: 4127-4133. (Pubitemid 36958432)
105. Viscomi MT, Oddi S, Latini L, Pasquariello N, Florenzano F, Bernardi G, et al,. (2009). Selective CB2 receptor agonism protects central neurons from remote axotomy-induced apoptosis through the PI3K/Akt pathway. J Neurosci 29: 4564-4570.
106. Walsh S, Mnich K, Mackie K, Gorman AM, Finn DP, Dowd E, (2010). Loss of cannabinoid CB1 receptor expression in the 6-hydroxydopamine-induced nigrostriatal terminal lesion model of Parkinson's disease in the rat. Brain Res Bull 81: 543-548.
107. Wang X, Michaelis EK, (2010). Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci 2: 12.
108. Wotherspoon G, Fox A, McIntyre P, Colley S, Bevan S, Winter J, (2005). Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons. Neuroscience 135: 235-245. (Pubitemid 41219752)
109. Wright S, (2007). Cannabinoid-based medicines for neurological disorders-clinical evidence. Mol Neurobiol 36: 129-136. (Pubitemid 351360352)
110. Yang L, Calingasan NY, Wille EJ, Cormier K, Smith K, Ferrante RJ, et al,. (2009). Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases. J Neurochem 109: 1427-1439.
111. Yiangou Y, Facer P, Durrenberger P, Chessell IP, Naylor A, Bountra C, et al,. (2006). COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol 6: 12.
112. Zhang J, Hoffert C, Vu HK, Groblewski T, Ahmad S, O'Donnell D, (2003). Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur J Neurosci 17: 2750-2754. (Pubitemid 36819300)
113. Zhang M, Martin BR, Adler MW, Razdan RK, Ganea D, Tuma RF, (2008). Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury. Neuroscience 152: 753-760.
114. Zuccato C, Valenza M, Cattaneo E, (2010). Molecular mechanisms and potential therapeutical targets in Huntington's disease. Physiol Rev 90: 905-981.