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Cannabinoids pp 479-507 | Cite as

Cannabinoid Control of Motor Function at the Basal Ganglia

  • J. Fernández-Ruiz
  • S. González
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 168)

Abstract

Classic and novel data strengthen the idea of a prominent role for the endocannabinoid signaling system in the control of movement. This finding is supported by three-fold evidence: (1) the abundance of the cannabinoid CB1 receptor subtype, but also of CB2 and vanilloid VR1 receptors, as well as of endocannabinoids in the basal ganglia and the cerebellum, the areas that control movement; (2) the demonstration of a powerful action, mostly of an inhibitory nature, of plant-derived, synthetic, and endogenous cannabinoids on motor activity, exerted by modulating the activity of various classic neurotransmitters; and (3) the occurrence of marked changes in endocannabinoid transmission in the basal ganglia of humans affected by several motor disorders, an event corroborated in animal models of these neurological diseases. This three-fold evidence has provided support to the idea that cannabinoid-based compounds, which act at key steps of the endocannabinoid transmission [receptors, transporter, fatty acid amide hydrolase (FAAH)], might be of interest because of their potential ability to alleviate motor symptoms and/or provide neuroprotection in a variety of neurological pathologies directly affecting basal ganglia structures, such as Parkinson’s disease and Huntington’s chorea, or indirectly, such as multiple sclerosis and Alzheimer’s disease. The present chapter will review the knowledge on this issue, trying to establish future lines for research into the therapeutic potential of the endocannabinoid system in motor disorders.

Keywords

Cannabinoids Cannabinoid receptors Movement Basal ganglia Motor disorders 

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References

  1. Alexi T, Hughes PE, Faull RLM, Williams LE (1998) 3-Nitropropionic acid’s lethal triplet: cooperative pathways of neurodegeneration. Neuroreport 9:57–64Google Scholar
  2. Anderson LA, Anderson JJ, Chase TN, Walters JR (1995) The cannabinoid agonists WIN55, 212-2 and CP55,940 attenuate rotational behaviour induced by a dopamine D1 but not D2 agonist in rats with unilateral lesions of the nigrostriatal pathway. Brain Res 691:106–114PubMedCrossRefGoogle Scholar
  3. Aroyo I, González S, Nuñez E, Lastres-Becker I, Sagredo O, Mechoulam R, Romero J, Ramos JA, Brouillet E, Fernández-Ruiz J (2005) Involvement of CB2 receptors in the neuroprotective effects of cannabinoids in rats with striatal atrophy induced by local application of malonate, an experimental model of Huntington’s disease. J Neurosci (submitted)Google Scholar
  4. Baker D, Pryce G (2003) The therapeutic potential of cannabis in multiple sclerosis. Expert Opin Investig Drugs 12:561–567PubMedGoogle Scholar
  5. Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Huffman JW, Layward L (2000) Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 404:84–87PubMedCrossRefGoogle Scholar
  6. Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di Marzo V (2001) Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J 15:300–302PubMedGoogle Scholar
  7. Beltramo M, Rodríguez de Fonseca F, Navarro M, Calignano A, Gorriti MA, Grammatikopoulos G, Sadile AG, Giuffrida A, Piomelli D (2000) Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor. J Neurosci 20:3401–3407PubMedGoogle Scholar
  8. Benito C, Nunez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ, Romero J (2003) Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23:11136–11141PubMedGoogle Scholar
  9. Berardelli A, Noth J, Thompson PD, Bollen EL, Curra A, Deuschl G, van Dijk JG, Topper R, Schwarz M, Roos RA (1999) Pathophysiology of chorea and bradykinesia in Huntington’s disease. Mov Disord 14:398–403PubMedCrossRefGoogle Scholar
  10. Berrendero F, Sánchez A, Cabranes A, Puerta C, Ramos JA, García-Merino A, Fernández-Ruiz J (2001) Changes in cannabinoid CB1 receptors in striatal and cortical regions of rats with experimental allergic encephalomyelitis, an animal model of multiple sclerosis. Synapse 41:195–202PubMedCrossRefGoogle Scholar
  11. Bisogno T, Berrendero F, Ambrosino G, Cebeira M, Ramos JA, Fernández-Ruiz JJ, Di Marzo V(1999) Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function. Biochem Biophys Res Commun 256:377–380PubMedCrossRefGoogle Scholar
  12. Blandini F, Nappi G, Tassorelli C, Martignoni E (2000) Functional changes in the basal ganglia circuitry in Parkinson’s disease. Prog Neurobiol 62:63–88PubMedCrossRefGoogle Scholar
  13. Brotchie JM (1998) Adjuncts to dopamine replacement: a pragmatic approach to reducing the problem of dyskinesia in Parkinson’s disease. Mov Disord 13:871–876PubMedCrossRefGoogle Scholar
  14. Brotchie JM (2000) The neural mechanisms underlying levodopa-induced dyskinesia in Parkinson’s disease. Ann Neurol 47:S105–S114PubMedGoogle Scholar
  15. Brotchie JM (2003) CB1 cannabinoid receptor signalling in Parkinson’s disease. Curr Opin Pharmacol 3:54–61PubMedGoogle Scholar
  16. Brouillet E, Conde F, Beal MF, Hantraye P (1999) ReplicatingHuntington’s disease phenotype in experimental animals. Prog Neurobiol 59:427–468PubMedCrossRefGoogle Scholar
  17. Cabranes A, Venderova K, de Lago E, Fezza F, Valenti M, Sánchez A, García-Merino A, Ramos JA, Di Marzo V, Fernández-Ruiz J (2005) Decreased endocannabinoid levels in the brain and beneficial effects of certain endocannabinoid uptake inhibitors in a rat model of multiple sclerosis: involvement of vanilloid TRPV1 receptors. Neurobiol Dis (in press)Google Scholar
  18. Cadogan AK, Alexander SP, Boyd EA, Kendall DA (1997) Influence of cannabinoids on electrically evoked dopamine release and cyclic AMP generation in the rat striatum. J Neurochem 69:1131–1137PubMedGoogle Scholar
  19. Carlsson A (2002) Treatment of Parkinson’s with L-DOPA. The early discovery phase, and a comment on current problems. J Neural Transm 109:777–787PubMedCrossRefGoogle Scholar
  20. Cattaneo E, Rigamonti D, Goffredo D, Zuccato C, Squitieri F, Sipione S (2001) Loss of normal huntingtin function: new developments inHuntington’s disease research. Trends Neurosci 24:182–188PubMedCrossRefGoogle Scholar
  21. Chan PK, Chan SC, Yung WH (1998) Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurones by a cannabinoid agonist. Neuroreport 9:671–675PubMedGoogle Scholar
  22. Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149PubMedGoogle Scholar
  23. Compton DR, Aceto MD, Lowe J, Martin BR (1996) In vivo characterization of a specific cannabinoid antagonis (SR141716A): inhibition of Δ9-tetrahydrocannabinol-induced responses and apparent agonist activity. J Pharmacol Exp Ther 277:586–594PubMedGoogle Scholar
  24. Consroe P (1998) Brain cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol Dis 5:534–551PubMedCrossRefGoogle Scholar
  25. Crawley JN, Corwin RL, Robinson JK, Felder ChC, Devane WA, Axelrod J (1993) Anandamide, an endogenous ligand of the cannabinoid receptor, induces hypomotility and hypothermia in vivo in rodents. Pharmacol Biochem Behav 46:967–972PubMedCrossRefGoogle Scholar
  26. de Lago E, Fernandez-Ruiz J, Ortega-Gutierrez S, Viso A, Lopez-Rodriguez ML, Ramos JA (2002) UCM707, a potent and selective inhibitor of endocannabinoid uptake, potentiates hypokinetic and antinociceptive effects of anandamide. Eur J Pharmacol 449:99–103PubMedGoogle Scholar
  27. de Lago E, Ligresti A, Ortar G, Morera E, Cabranes A, Pryce G, Bifulco M, Baker D, Fernandez-Ruiz J, Di Marzo V (2004a) In vivo pharmacological actions of two novel inhibitors of anandamide cellular uptake. Eur J Pharmacol 484:249–257PubMedGoogle Scholar
  28. de Lago E, de Miguel, Lastres-Becker I, Ramos JA, Fernández-Ruiz J (2004b) Involvement of vanilloid-like receptors in the effects of anandamide on motor behavior and nigrostriatal dopaminergic activity: in vivo and in vitro evidence. Brain Res 1007:152–159PubMedGoogle Scholar
  29. de Lago E, Ortega S, López-Rodríguez ML, Ramos JA, Fernández-Ruiz J (2004c) Therapeutic potential of UCM707, an inhibitor of the endocannabinoid transport, in animal models of various neurological diseases. Mov Disord (submitted)Google Scholar
  30. 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 98:705–713PubMedCrossRefGoogle Scholar
  31. Desarnaud F, Cadas H, Piomelli D (1995) Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial purification. J Biol Chem 270:6030–6035PubMedGoogle Scholar
  32. Dewey WL (1986) Cannabinoid pharmacology. Pharmacol Rev 38:151–178PubMedGoogle Scholar
  33. Di Marzo V, Melck D, Bisogno T, De Petrocellis L (1998) Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 21:521–528PubMedGoogle Scholar
  34. Di Marzo V, Hill MP, Bisogno T, Crossman AR, Brotchie JM (2000a) Enhanced levels of endocannabinoids in the globus pallidus are associated with a reduction in movement in an animal model of Parkinson’s disease. FASEB J 14:1432–1438PubMedGoogle Scholar
  35. Di Marzo V, Berrendero F, Bisogno T, Gonzalez S, Cavaliere P, Romero J, Cebeira M, Ramos JA, Fernandez-Ruiz J (2000b) Enhancement of anandamide formation in the limbic forebrain and reduction of endocannabinoid contents in the striatum of Δ9-tetrahydrocannabinol-tolerant rats. J Neurochem 74:1627–1635PubMedGoogle Scholar
  36. Di Marzo V, Lastres-Becker I, Bisogno T, De Petrocellis L, Milone A, Davis JB, Fernandez-Ruiz J (2001) Hypolocomotor effects in rats of capsaicin and two long chain capsaicin homologues. Eur J Pharmacol 420:123–131PubMedGoogle Scholar
  37. Dinh TP, Freund TF, Piomelli D (2002) A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chem Phys Lipids 121:149–158PubMedCrossRefGoogle Scholar
  38. Factor SA, Friedman JH (1997) The emerging role of clozapine in the treatment of movement disorders. Mov Disord 12:483–496PubMedGoogle Scholar
  39. Fernández-Espejo E, Caraballo I, Rodriguez de Fonseca F, El Banoua F, Ferrer B, Flores JA, Galan-Rodriguez B (2004) Homeostatic changes of anandamide synthesis, and functional effects of cannabinoid CB1 antagonists in rats with severe hemiparkinsonism. Neurobiol Dis (in press)Google Scholar
  40. Fernandez-Ruiz J, Lastres-Becker I, Cabranes A, Gonzalez S, Ramos JA (2002) Endocannabinoids and basal ganglia functionality. Prostaglandins Leukot Essent Fatty Acids 66:263–273Google Scholar
  41. Ferrer B, Asbrock N, Kathuria S, Piomelli D, Giuffrida A (2003) Effects of levodopa on endocannabinoid levels in rat basal ganglia: implications for the treatment of levodopainduced dyskinesias. Eur J Neurosci 18:1607–1614PubMedCrossRefGoogle Scholar
  42. Fox SH, Henry B, Hill M, Crossman A, Brotchie J (2002a) Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 17:1180–1187PubMedGoogle Scholar
  43. Fox SH, Kellett M, Moore AP, Crossman AR, Brotchie JM (2002b) Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord 17:145–149PubMedGoogle Scholar
  44. Francis PT, Webster MT, Chesell IP, Holmes C, Stratmann GC, Procter AW, Cross AJ, Green AR, Bouen DM (1993) Neurotransmitters and second messengers in aging and Alzheimer’s disease. Ann NY Acad Sci 695:19–26PubMedGoogle Scholar
  45. Fride E, Mechoulam R (1993) Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol 231:313–314PubMedCrossRefGoogle Scholar
  46. Gerdeman G, Lovinger DM (2001) CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. J Neurophysiol 85:468–471PubMedGoogle Scholar
  47. Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2:358–363PubMedGoogle Scholar
  48. Giuffrida A, Beltramo M, Piomelli D (2001) Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology. J Pharmacol Exp Ther 298:7–14PubMedGoogle Scholar
  49. Glaser ST, Abumrad NA, Fatade F, Kaczocha M, Studholme KM, Deutsch DG (2003) Evidence against the presence of an anandamide transporter. Proc Natl Acad Sci USA 100:4269–4274PubMedCrossRefGoogle Scholar
  50. Glass M, Faull RLM, Dragunow M (1993) Loss of cannabinoid receptors in the substantia nigra in Huntington’s disease. Neuroscience 56:523–527PubMedCrossRefGoogle Scholar
  51. 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 97:505–519PubMedCrossRefGoogle Scholar
  52. González S, Romero J, de Miguel R, Lastres-Becker I, Villanúa MA, Makriyannis A, Ramos JA, Fernández-Ruiz J (1999) Extrapyramidal and neuroendocrine effects of AM404, an inhibitor of the carrier-mediated transport of anandamide. Life Sci 65:327–336PubMedGoogle Scholar
  53. Gorriti MA, Rodríguez de Fonseca F, Navarro M, Palomo T (1999) Chronic (-)Δ9-tetrahydrocannabinol treatment induces sensitization to the psychomotor effects of amphetamine in rats. Eur J Pharmacol 365:133–142PubMedCrossRefGoogle Scholar
  54. Grundy RI (2002) The therapeutic potential of the cannabinoids in neuroprotection. Expert Opin Investig Drugs 11:1365–1374PubMedCrossRefGoogle Scholar
  55. Gubellini P, Picconi B, Bari M, Battista N, Calabresi P, Centonze D, Bernardi G, Finazzi-Agro A, Maccarrone M (2002) Experimental parkinsonism alters endocannabinoid degradation: implications for striatal glutamatergic transmission. J Neurosci 22:6900–6907PubMedGoogle Scholar
  56. Gueudet C, Santucci V, Rinaldi-Carmona M, Soubrie P, Le Fur G (1995) The CB1 cannabinoid receptor antagonist SR141716A affects A9 dopamine neuronal activity in the rats. Neuroreport 6:1421–1425PubMedGoogle Scholar
  57. Hemming M, Yellowlees PM (1993) Effective treatment of Tourette’s syndrome with marijuana. J Psychopharmacol 7:389–391Google Scholar
  58. Herkenham M, Lynn AB, Little MD, Melvin LS, Johnson MR, de Costa DR, Rice KC (1991a) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11:563–583PubMedGoogle Scholar
  59. Herkenham M, Lynn AB, de Costa BR, Richfield EK (1991b) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547:267–274PubMedCrossRefGoogle Scholar
  60. Hersch SM, Ferrante RJ (1997) Neuropathology and pathophysiology of Huntington’s disease. In: Watts RL, Koller WC (eds) Movement disorders. Neurologic principles and practice. McGraw-Hill, New York, pp 503–518Google Scholar
  61. Hiltunen AJ, Jarbe TU, Wangdahl K (1988) Cannabinol and cannabidiol in combination: temperature, open-field activity, and vocalization. Pharmacol Biochem Behav 30:675–678PubMedCrossRefGoogle Scholar
  62. Hohmann AG, Herkenham M (2000) Localization of cannabinoid CB1 receptor mRNA in neuronal subpopulations of rat striatum: a double-label in situ hybridization study. Synapse 37:71–80PubMedCrossRefGoogle Scholar
  63. Itier JM, Ibanez P, Mena MA, Abbas N, Cohen-Salmon C, Bohme GA, Laville M, Pratt J, Corti O, Pradier L, Ret G, Joubert C, Periquet M, Araujo F, Negroni J, Casarejos MJ, Canals S, Solano R, Serrano A, Gallego E, Sanchez M, Denefle P, Benavides J, Tremp G, Rooney TA, Brice A, Garcia de Yebenes J (2003) Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 12:2277–2291PubMedCrossRefGoogle Scholar
  64. Iuvone T, Esposito G, Esposito R, Santamaria R, Di Rosa M, Izzo AA (2004) Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on betaamyloid-induced toxicity in PC12 cells. J Neurochem 89:134–141PubMedGoogle Scholar
  65. Iversen L (2003) Cannabis and the brain. Brain 126:1252–1270PubMedCrossRefGoogle Scholar
  66. Jarbe TU, Sheppard R, Lamb RJ, Makriyannis A, Lin S, Goutopoulos A (1998) Effects of Δ9-tetrahydrocannabinol and (R)-methanandamide on open-field behavior in rats. Behav Pharmacol 9:169–174PubMedGoogle Scholar
  67. Kieburtz K (1999) Antiglutamate therapies in Huntington’s disease. J Neural Transm Suppl 55:97–102PubMedGoogle Scholar
  68. Kurlan R, Richard IH, Papka M, Marshall F (2000) Movement disorders in Alzheimer’s disease: more rigidity of definitions is needed. Mov Disord 15:24–29PubMedCrossRefGoogle Scholar
  69. Lastres-Becker I, Cebeira M, de Ceballos M, Zeng B-Y, Jenner P, Ramos JA, Fernández-Ruiz J (2001a) Increased cannabinoid CB1 receptor binding and activation of GTP-binding proteins in the basal ganglia of patientswith Parkinson’s syndromeand ofMPTP-treated marmosets. Eur J Neurosci 14:1827–1832PubMedCrossRefGoogle Scholar
  70. Lastres-Becker I, Fezza F, Cebeira M, Bisogno T, Ramos JA, Milone A, Fernández-Ruiz JJ, Di Marzo V (2001b) Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington’s disease. Neuroreport 12:2125–2129PubMedGoogle Scholar
  71. Lastres-Becker I, Hansen HH, Berrendero F, de Miguel R, Pérez-Rosado A, Manzanares J, Ramos JA, Fernández-Ruiz J (2002a) Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington’s disease. Synapse 44:23–35PubMedCrossRefGoogle Scholar
  72. Lastres-Becker I, Gomez M, De Miguel R, Ramos JA, Fernández-Ruiz J (2002b) Loss of cannabinoid CB1 receptors in the basal ganglia in the late akinetic phase of rats with experimental Huntington’s disease. Neurotox Res 4:601–608PubMedCrossRefGoogle Scholar
  73. Lastres-Becker I, Berrendero F, Lucas JJ, Martin-Aparicio E, Yamamoto A, Ramos JA, Fernández-Ruiz J (2002c) Loss of mRNA levels, binding and activation of GTP-binding proteins for cannabinoid CB1 receptors in the basal ganglia of a transgenic model of Huntington;’s disease. Brain Res 929:236–242PubMedCrossRefGoogle Scholar
  74. Lastres-Becker I, de Miguel R, De Petrocellis L, Makriyannis A, Di Marzo V, Fernández-Ruiz J (2003a) Compounds acting at the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington’s disease. J Neurochem 84:1097–1109PubMedCrossRefGoogle Scholar
  75. Lastres-Becker I, De Miguel R, Fernández-Ruiz J (2003b) The endocannabinoid system and Huntington’s disease. Curr Drug Target CNS Neurol Disord 2:335–347Google Scholar
  76. Lastres-Becker I, Bizat N, Boyer F, Hantraye P, Brouillet E, Fernández-Ruiz J (2003c) Effects of cannabinoids in the rat model of Huntington’s disease generated by an intrastriatal injection of malonate. Neuroreport 14:813–816PubMedGoogle Scholar
  77. Lastres-Becker I, Molina-Holgado F, Ramos JA, Mechoulam R, Fernández-Ruiz J (2004a) Cannabinoids provide neuroprotection in experimental models of Parkinson’s disease: involvement of their antioxidant properties and/or of glial cell-mediated effects. Neurobiol Dis (in press)Google Scholar
  78. Lastres-Becker I, Bizat N, Boyer F, Hantraye P, Fernández-Ruiz J, Brouillet E (2004b) Potential involvement of cannabinoid receptors in 3-nitropropionic acid toxicity in vivo: implication for Huntington’s disease. Neuroreport 15:2375–2379PubMedGoogle Scholar
  79. Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Böhme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283:401–404PubMedCrossRefGoogle Scholar
  80. Maccarrone M, Gubellini P, Bari M, Picconi B, Battista N, Centonze D, Bernardi G, Finazzi-Agro A, Calabresi P (2003) Levodopa treatment reverses endocannabinoid system abnormalities in experimental parkinsonism. J Neurochem 85:1018–1025PubMedCrossRefGoogle Scholar
  81. Mailleux P, Vanderhaeghen JJ (1992a) Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization histochemistry. Neuroscience 48:655–668PubMedCrossRefGoogle Scholar
  82. Mailleux P, Vanderhaeghen JJ (1992b) Age-related loss of cannabinoid of cannabinoid receptor binding sites and mRNA in the rat striatum. Neurosci Lett 147:179–181PubMedGoogle Scholar
  83. Mailleux P, Vanderhaeghen JJ (1993) Dopaminergic regulation of cannabinoid receptor mRNA levels in the rat caudate-putamen: an in situ hybridization study. J Neurochem 61:1705–1712PubMedGoogle Scholar
  84. Maneuf YP, Nash JE, Croosman AR, Brotchie JM (1996) Activation of the cannabinoid receptor by Δ9-THC reduces GABA uptake in the globus pallidus. Eur J Pharmacol 308:161–164PubMedCrossRefGoogle Scholar
  85. Maneuf YP, Croosman AR, Brotchie JM (1997) The cannabinoid receptor agonist WIN 55,212-2 reduces D2, but not D1, dopamine receptor-mediated alleviation of akinesia in the reserpine-treated rat model of Parkinson’s disease. Exp Neurol 148:265–270PubMedCrossRefGoogle Scholar
  86. McLaughlin PJ, Delevan CE, Carnicom S, Robinson JK, Brener J (2000) Fine motor control in rats is disrupted by Δ9-tetrahydrocannabinol. Pharmacol Biochem Behav 66:803–809PubMedCrossRefGoogle Scholar
  87. Meschler JP, Howlett AC (2001) Signal transduction interactions between CB1 cannabinoid and dopamine receptors in the rat and monkey striatum. Neuropharmacology 40:918–926PubMedCrossRefGoogle Scholar
  88. Meschler JP, Howlett AC, Madras BK (2001) Cannabinoid receptor agonist and antagonist effects on motor function in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human primates. Psychopharmacology (Berl) 156:79–85PubMedCrossRefGoogle Scholar
  89. Mezey E, Toth ZE, Cortright DN, Arzubi MK, Krause JE, El de R, Guo A, Blumberg PM, Szallasi A (2000) Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci USA 97:3655–3660PubMedCrossRefGoogle Scholar
  90. Miller A, Walker JM (1995) Effects of a cannabinoid on spontaneous and evoked neuronal activity in the substantia nigra pars reticulata. Eur J Pharmacol 279:179–185PubMedCrossRefGoogle Scholar
  91. Miller A, Walker JM (1996) Electrophysiological effects of a cannabinoid on neural activity in the globus pallidus. Eur J Pharmacol 304:29–35PubMedCrossRefGoogle Scholar
  92. Miller A, Sañudo-Peña MC, Walker JM (1998) Ipsilateral turning behavior induced by unilateral microinjections of a cannabinoid into the rat subthalamic nucleus. Brain Res 793:7–11PubMedCrossRefGoogle Scholar
  93. Milton NG (2002) Anandamide and noladin ether prevent neurotoxicity of the human amyloid-beta peptide. Neurosci Lett 332:127–130PubMedCrossRefGoogle Scholar
  94. Moss DE, McMaster SB, Rogers J (1981) Tetrahydrocannabinol potentiates reserpine-induced hypokinesia. Pharmacol Biochem Behav 15:779–783PubMedCrossRefGoogle Scholar
  95. Müller-Vahl KR (2003) Cannabinoids reduce symptoms of Tourette’s syndrome. Expert Opin Pharmacother 4:1717–1725PubMedGoogle Scholar
  96. Müller-Vahl KR, Kolbe H, Schneider U, Emrich HM (1998) Cannabinoids: possible role in the pathophysiology of Gilles de la Tourette-syndrome. Acta Psychiatr Scand 98:502–506PubMedGoogle Scholar
  97. Müller-Vahl KR, Schneider U, Kolbe H, Emrich HM (1999a) Treatment of Tourette-syndrome with Δ9-tetrahydrocannabinol. Am J Psychiatry 156:495PubMedGoogle Scholar
  98. Müller-Vahl KR, Schneider U, Emrich HM (1999b) Nabilone increases choreatic movements in Huntington’s disease. Mov Disord 14:1038–1040PubMedGoogle Scholar
  99. Müller-Vahl KR, Kolbe H, Schneider U, Emrich HM (1999c) Cannabis in movement disorders. Forsch Komplementarmed 6:23–27PubMedGoogle Scholar
  100. Müller-Vahl KR, Schneider U, Koblenz A, Jobges M, Kolbe H, Daldrup T, Emrich HM (2002) Treatment of Tourette’s syndrome with Δ9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry 35:57–61PubMedGoogle Scholar
  101. Navarro M, Fernández-Ruiz JJ, de Miguel R, Hernández ML, Cebeira M, Ramos JA (1993) Motor disturbances induced by an acute dose of Δ9-tetrahydrocannabinol: possible involvement of nigrostriatal dopaminergic alterations. Pharmacol Biochem Behav 45:291–298PubMedCrossRefGoogle Scholar
  102. Nuñez E, Benito C, Pazos MR, Barbachano A, Fajardo O, González S, Tolón R, Romero J (2004) Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study. Synapse 53:208–213PubMedGoogle Scholar
  103. Page KJ, Besret L, Jain M, Monaghan EM, Dunnett BS, Everitt BJ (2000) Effects of systemic 3-nitropropionic acid-induced lesions of the dorsal striatum on cannabinoid and muopioid receptor binding in the basal ganglia. Exp Brain Res 130:142–150PubMedCrossRefGoogle Scholar
  104. Pazos MR, Nuñez E, Benito C, Tolón R, Romero J (2004) Role of the endocannabinoid system in Alzheimer’s disease: new perspectives. Life Sci 75:1907–1915PubMedCrossRefGoogle Scholar
  105. Pertwee RG (2002) Cannabinoids and multiple sclerosis. Pharmacol Ther 95:165–174PubMedCrossRefGoogle Scholar
  106. Pertwee RG, Greentree SG, Swift PA (1988) Drugs which stimulate or facilitate central GABAergic transmission interact synergistically with Δ9-tetrahydrocannabinol to produce marked catalepsy in mice. Neuropharmacology 27:1265–1270PubMedGoogle Scholar
  107. Reddy PH, Williams M, Tagle DA (1999) Recent advances in understanding the pathogenesis of Huntington’s disease. Trends Neurosci 22:248–255PubMedCrossRefGoogle Scholar
  108. Richfield EK, Herkenham M (1994) Selective vulnerability in Huntington’s disease: preferential loss of cannabinoid receptors in lateral globus pallidus. Ann Neurol 36:577–584PubMedCrossRefGoogle Scholar
  109. Richter A, Loscher W (1994) (+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters. Eur J Pharmacol 264:371–377PubMedGoogle Scholar
  110. Richter A, Loscher W (2002) Effects of pharmacological manipulations of cannabinoid receptors on severity of dystonia in a genetic model of paroxysmal dyskinesia. Eur J Pharmacol 454:145–151PubMedCrossRefGoogle Scholar
  111. Rodriguez de Fonseca F, Gorriti MA, Fernández-Ruiz J, Palomo T, Ramos JA (1994) Down-regulation of rat brain cannabinoid binding sites after chronic Δ9-tetrahydrocannabinol treatment. Pharmacol Biochem Behav 47:33–40Google Scholar
  112. Romero J, García L, Cebeira M, Zadrozny D, Fernández-Ruiz J, Ramos JA (1995a) The endogenous cannabinoid receptor ligand, anandamide, inhibits the motor behaviour: role of nigrostriatal dopaminergic neurons. Life Sci 56:2033–2040PubMedCrossRefGoogle Scholar
  113. Romero J, de Miguel R, García-Palomero E, Fernández-Ruiz J, Ramos JA (1995b) Time-course of the effects of anandamide, the putative endogenous cannabinoid receptor ligand, on extrapyramidal function. Brain Res 694:223–232PubMedCrossRefGoogle Scholar
  114. Romero J, García-Palomero E, Lin SY, Ramos JA, Makriyannis A, Fernández-Ruiz J (1996a) Extrapyramidal effects of methanandamide, an analog of anandamide, the endogenous CB1 receptor ligand. Life Sci 58:1249–1257PubMedCrossRefGoogle Scholar
  115. Romero J, García-Palomero E, Fernández-Ruiz J, Ramos JA (1996b) Involvement of GABA-B receptors in the motor inhibition produced by agonists of brain cannabinoid receptors. Behav Pharmacol 7:299–302PubMedGoogle Scholar
  116. Romero J, de Miguel R, Ramos JA, Fernández-Ruiz J (1998a) The activation of cannabinoid receptors in striatonigral neurons inhibited GABA uptake. Life Sci 62:351–363PubMedGoogle Scholar
  117. Romero J, Berrendero F, García-Gil L, de la Cruz P, Ramos JA, Fernández-Ruiz J (1998b) Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist-stimulated [35S]-GTPγS binding in the basal ganglia of aged rats. Neuroscience 84:1075–1083PubMedCrossRefGoogle Scholar
  118. Romero J, Berrendero F, Perez-Rosado A, Manzanares J, Rojo A, Fernández-Ruiz J, de Yébenes JG, Ramos JA (2000) Unilateral 6-hydroxydopamine lesions of nigrostriatal dopaminergic neurons increased CB1 receptor mRNA levels in the caudate-putamen. Life Sci 66:485–494PubMedCrossRefGoogle Scholar
  119. Romero J, Lastres-Becker I, de Miguel R, Berrendero F, Ramos JA, Fernández-Ruiz J (2002) The endogenous cannabinoid system and the basal ganglia. biochemical, pharmacological, and therapeutic aspects. Pharmacol Ther 95:137–152PubMedCrossRefGoogle Scholar
  120. Sakurai-Yamashita Y, Kataoka Y, Fujiwara M, Mine K, Ueki S (1989) Δ9-Tetrahydrocannabinol facilitates striatal dopaminergic transmission. Pharmacol Biochem Behav 33:397–400PubMedGoogle Scholar
  121. Sañudo-Peña MC, Walker JM (1997) Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat. J Neurophysiol 77:1635–1638PubMedGoogle Scholar
  122. Sañudo-Peña MC, Patrick SL, Khen S, Patrick RL, Tsou K, Walker JM (1998) Cannabinoid effects in basal ganglia in a rat model of Parkinson’s disease. Neurosci Lett 248:171–174PubMedGoogle Scholar
  123. Sañudo-Peña MC, Tsou K, Walker JM (1999) Motor actions of cannabinoids in the basal ganglia output nuclei. Life Sci 65:703–713PubMedGoogle Scholar
  124. Sañudo-Peña MC, Romero J, Seale GE, Fernández-Ruiz J, Walker JM (2000) Activational role of cannabinoids on movement. Eur J Pharmacol 391:269–274PubMedGoogle Scholar
  125. Schut LJ (1998) Motor system changes in the aging brain: what is normal and what is not. Geriatrics 53:S16–S19PubMedGoogle Scholar
  126. Segovia G, Mora F, Crossman AR, Brotchie JM (2003) Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high-dose levodopa in the reserpine-treated rat model of Parkinson’s disease. Mov Disord 18:138–149PubMedCrossRefGoogle Scholar
  127. 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 57:2108–2111PubMedGoogle Scholar
  128. Silverdale MA, McGuire S, McInnes A, Crossman AR, Brotchie JM (2001) Striatal cannabinoid CB1 receptor mRNA expression is decreased in the reserpine-treated rat model of Parkinson’s disease. Exp Neurol 169:400–406PubMedCrossRefGoogle Scholar
  129. Skaper SD, Buriani A, Dal Toso R, Petrelli L, Romanello S, Facci L, Leon A (1996) The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proc Natl Acad Sci USA 93:3984–3989PubMedCrossRefGoogle Scholar
  130. Smith PB, Compton DR, Welch SP, Razdan RK, Mechoulam R, Martin BR (1994) The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice. J Pharmacol Exp Ther 270:219–227PubMedGoogle Scholar
  131. Souilhac J, Poncelet M, Rinaldi-Carmona M, Le-Fur G, Soubrie P (1995) Intrastriatal injection of cannabinoid receptor agonists induced turning behavior in mice. Pharmacol Biochem Behav 51:3–7PubMedCrossRefGoogle Scholar
  132. Szabo B, Dorner L, Pfreundtner C, Norenberg W, Starke K (1998) Inhibition of GABAergic inhibitory postsynaptic currents by cannabinoids in rat corpus striatum. Neuroscience 85:395–403PubMedCrossRefGoogle Scholar
  133. Szabo B, Muller T, Koch H (1999) Effects of cannabinoids on dopamine release in the corpus striatum and the nucleus accumbens in vitro. J Neurochem 73:1084–1089PubMedCrossRefGoogle Scholar
  134. Szabo B, Wallmichrath I, Mathonia P, Pfreundtner C (2000) Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata. Neuroscience 97:89–97PubMedCrossRefGoogle Scholar
  135. Tersigni TJ, Rosenberg HC (1996) Local pressure application of cannabinoid agonists increases spontaneous activity of rat substantia nigra pars reticulata neurons without affecting response to iontophoretically-applied GABA. Brain Res 733:184–192PubMedCrossRefGoogle Scholar
  136. Tsou K, Brown S, Sañudo-Peña MC, Mackie K, Walker JM (1998a) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83:393–411PubMedGoogle Scholar
  137. Tsou K, Nogueron MI, Muthian S, Sañudo-Peña M, Hillard CJ, Deutsch DG, Walker JM (1998b) Fatty acid amide hydrolase is located preferentially in large neurons in the rat central nervous system as revealed by immunohistochemistry. Neurosci Lett 254:137–140PubMedCrossRefGoogle Scholar
  138. van der Stelt M, Di Marzo V (2003) The endocannabinoid system in the basal ganglia and in the mesolimbic reward system: implications for neurological and psychiatric disorders. Eur J Pharmacol 480:133–150PubMedGoogle Scholar
  139. Westlake TM, Howlett AC, Bonner TI, Matsuda LA, Herkenham M (1994) Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer’s brains. Neuroscience 63:637–652PubMedCrossRefGoogle Scholar
  140. Wickens AP, Pertwee RG (1993) Δ9-Tetrahydrocannabinol and anandamide enhance the ability of muscimol to induce catalepsy in the globus pallidus of rats. Eur J Pharmacol 250:205–208PubMedCrossRefGoogle Scholar
  141. Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A (2003) Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 362:1517–1526PubMedCrossRefGoogle Scholar
  142. Zaretsky A, Rector NA, Seeman MV, Fornazzari X (1993) Current cannabis use and tardive dyskinesia. Schizophr Res 11:3–8PubMedCrossRefGoogle Scholar
  143. Zeng BY, Dass B, Owen A, Rose S, Cannizzaro C, Tel BC, Jenner P (1999) Chronic LDOPA treatment increases striatal cannabinoid CB1 receptor mRNA expression in 6-hydroxydopamine-lesioned rats. Neurosci Lett 276:71–74PubMedCrossRefGoogle Scholar
  144. Zimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI (1999) Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 96:5780–5785PubMedCrossRefGoogle Scholar
  145. Zygmunt PM, Chuang H, Movahed P, Julius D, Hogestatt ED (2000) The anandamide transport inhibitor AM404 activates vanilloid receptors. Eur J Pharmacol 396:39–42PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • J. Fernández-Ruiz
    • 1
  • S. González
    • 1
  1. 1.Departamento de Bioquímica y Biología Molecular III, Facultad de MedicinaUniversidad Complutense, Ciudad Universitaria s/nMadridSpain

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