Skip to main content
SpringerLink
Log in

Dopamine–Endocannabinoid Interactions in Parkinson’s Disease

  • Chapter
  • First Online:
Cortico-Subcortical Dynamics in Parkinson's Disease

Part of the book series: Contemporary Neuroscience ((CNEURO))

  • 736 Accesses

Cannabinoids have been used for medicinal purposes for millennia, functioning as analgesics and anxiolytics but also treating disorders ranging from constipation and digestive ailments to arthritis and malaria. For this reason, it is quite understandable that since their discovery 15 years ago, researchers have explored the uses of endogenous cannabinoids (eCBs) in the same manner. eCBs, lipophilic signaling molecules, affect the signaling of many neurotransmitter systems, and their modulation of dopamine neurotransmission, in particular, has relevance for treating conditions ranging from addiction to movement disorders such as Huntington’s and Parkinson’s diseases. In the following chapter, we will characterize the relationship between eCBs and dopamine in the nigrostriatal pathway, detailing both dopaminergic modulation of eCBs and the effect of eCBs and CB1 receptor ligands on dopaminergic transmission. The efficacy of CB1 receptor modulating drugs for the treatment of Parkinson’s disease has been examined in several animal models of the disease. However, to date, it remains undetermined whether eCBs serve as neuroprotective agents or rather, potentiate dopaminergic loss associated with Parkinson’s disease (PD). We will discuss interactions between eCBs and dopamine neurons, and propose, based on compelling evidence of eCB modulation of dopaminergic transmission, that CB1 receptor antagonists are better suited for the treatment of PD.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346(6284):561–4.

    Article  PubMed  CAS  Google Scholar 

  2. Herkenham M, Groen BG, Lynn AB, De Costa BR, Richfield EK. Neuronal localization of cannabinoid receptors and second messengers in mutant mouse cerebellum. Brain Res 1991;552(2):301–10.

    Article  PubMed  CAS  Google Scholar 

  3. Howlett AC, Bidaut-Russell M, Devane WA, Melvin LS, Johnson MR, Herkenham M. The cannabinoid receptor: biochemical, anatomical and behavioral characterization. Trends Neurosci 1990;13(10):420–3.

    Article  PubMed  CAS  Google Scholar 

  4. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science (New York, NY) 1992;258(5090):1946–9.

    Article  CAS  Google Scholar 

  5. Fride E, Mechoulam R. Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol 1993;231(2):313–4.

    Article  PubMed  CAS  Google Scholar 

  6. Felder CC, Briley EM, Axelrod J, Simpson JT, Mackie K, Devane WA. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc Natl Acad Sci U S A 1993;90(16):7656–60.

    Article  PubMed  CAS  Google Scholar 

  7. Poling JS, Rogawski MA, Salem N, Jr., Vicini S. Anandamide, an endogenous cannabinoid, inhibits Shaker-related voltage-gated K+ channels. Neuropharmacology 1996;35(7):983–91.

    Article  PubMed  CAS  Google Scholar 

  8. Hampson AJ, Bornheim LM, Scanziani M, et al. Dual effects of anandamide on NMDA receptor-mediated responses and neurotransmission. J Neurochem 1998;70(2):671–6.

    Article  PubMed  CAS  Google Scholar 

  9. Twitchell W, Brown S, Mackie K. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol 1997;78(1):43–50.

    PubMed  CAS  Google Scholar 

  10. Adams IB, Ryan W, Singer M, Razdan RK, Compton DR, Martin BR. Pharmacological and behavioral evaluation of alkylated anandamide analogs. Life Sci 1995;56(23–24):2041–8.

    Article  PubMed  CAS  Google Scholar 

  11. Vogel Z, Barg J, Levy R, Saya D, Heldman E, Mechoulam R. Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. J Neurochem 1993;61(1):352–5.

    Article  PubMed  CAS  Google Scholar 

  12. Romero J, de Miguel R, Garcia-Palomero E, Fernandez-Ruiz JJ, Ramos JA. Time-course of the effects of anandamide, the putative endogenous cannabinoid receptor ligand, on extrapyramidal function. Brain Res 1995;694(1–2):223–32.

    Article  PubMed  CAS  Google Scholar 

  13. Souilhac J, Poncelet M, Rinaldi-Carmona M, Le Fur G, Soubrie P. Intrastriatal injection of cannabinoid receptor agonists induced turning behavior in mice. Pharmacol Biochem Behav 1995;51(1):3–7.

    Article  PubMed  CAS  Google Scholar 

  14. Fride E, Barg J, Levy R, et al. Low doses of anandamides inhibit pharmacological effects of delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther 1995;272(2):699–707.

    PubMed  CAS  Google Scholar 

  15. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50(1):83–90.

    Article  PubMed  CAS  Google Scholar 

  16. Di Tomaso E, Cadas H, Gaillet S, et al. Endogenous lipids that activate cannabinoid receptors. Formation and inactivation. Adv Exp Med Biol 1997;407:335–40.

    PubMed  Google Scholar 

  17. Bisogno T, Sepe N, Melck D, Maurelli S, De Petrocellis L, Di Marzo V. Biosynthesis, release and degradation of the novel endogenous cannabimimetic metabolite 2-arachidonoylglycerol in mouse neuroblastoma cells. Biochem J 1997;322 (Pt 2):671–7.

    PubMed  CAS  Google Scholar 

  18. Beltramo M, Stella N, Calignano A, Lin SY, Makriyannis A, Piomelli D. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science (New York, NY) 1997;277(5329):1094–7.

    Article  CAS  Google Scholar 

  19. Hillard CJ, Edgemond WS, Jarrahian A, Campbell WB. Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule cells occurs via facilitated diffusion. J Neurochem 1997;69(2):631–8.

    Article  PubMed  CAS  Google Scholar 

  20. Piomelli D, Beltramo M, Glasnapp S, et al. Structural determinants for recognition and translocation by the anandamide transporter. Proc Natl Acad Sci U S A 1999;96(10):5802–7.

    Article  PubMed  CAS  Google Scholar 

  21. Moore SA, Nomikos GG, Dickason-Chesterfield AK, et al. Identification of a high-affinity binding site involved in the transport of endocannabinoids. Proc Natl Acad Sci U S A 2005;102(49):17852–7.

    Article  PubMed  CAS  Google Scholar 

  22. Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 1996;384(6604):83–7.

    Article  PubMed  CAS  Google Scholar 

  23. Hillard CJ, Wilkison DM, Edgemond WS, Campbell WB. Characterization of the kinetics and distribution of N-arachidonylethanolamine (anandamide) hydrolysis by rat brain. Biochimica et biophysica acta 1995;1257(3):249–56.

    PubMed  Google Scholar 

  24. McKinney MK, Cravatt BF. Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 2005;74:411–32.

    Article  PubMed  CAS  Google Scholar 

  25. Dinh TP, Carpenter D, Leslie FM, et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci U S A 2002;99(16):10819–24.

    Article  PubMed  CAS  Google Scholar 

  26. Chevaleyre V, Takahashi KA, Castillo PE. Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 2006;29:37–76.

    Article  PubMed  CAS  Google Scholar 

  27. Wilson RI, Nicoll RA. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 2001;410(6828):588–92.

    Article  PubMed  CAS  Google Scholar 

  28. Diana MA, Levenes C, Mackie K, Marty A. Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids. J Neurosci 2002;22(1):200–8.

    PubMed  CAS  Google Scholar 

  29. Kreitzer AC, Regehr WG. Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. J Neurosci 2001;21(20):RC174.

    PubMed  CAS  Google Scholar 

  30. Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 2001;29(3):717–27.

    Article  PubMed  CAS  Google Scholar 

  31. Ohno-Shosaku T, Maejima T, Kano M. Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 2001;29(3):729–38.

    Article  PubMed  CAS  Google Scholar 

  32. Yoshida T, Hashimoto K, Zimmer A, Maejima T, Araishi K, Kano M. The cannabinoid CB1 receptor mediates retrograde signals for depolarization-induced suppression of inhibition in cerebellar Purkinje cells. J Neurosci 2002;22(5):1690–7.

    PubMed  CAS  Google Scholar 

  33. Brown SP, Brenowitz SD, Regehr WG. Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nat Neurosci 2003;6(10):1048–57.

    Article  PubMed  CAS  Google Scholar 

  34. Maejima T, Ohno-Shosaku T, Kano M. Endogenous cannabinoid as a retrograde messenger from depolarized postsynaptic neurons to presynaptic terminals. Neurosci Res 2001;40(3):205–10.

    Article  PubMed  CAS  Google Scholar 

  35. Melis M, Perra S, Muntoni AL, et al. Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons. J Neurosci 2004;24(47):10707–15.

    Article  PubMed  CAS  Google Scholar 

  36. Gerdeman GL, Ronesi J, Lovinger DM. Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci 2002;5(5):446–51.

    PubMed  CAS  Google Scholar 

  37. Robbe D, Kopf M, Remaury A, Bockaert J, Manzoni OJ. Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. Proc Natl Acad Sci U S A 2002;99(12):8384–8.

    Article  PubMed  CAS  Google Scholar 

  38. Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron 2004;44(1):5–21.

    Article  PubMed  CAS  Google Scholar 

  39. Surmeier DJ, Ding J, Day M, Wang Z, Shen W. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 2007;30(5):228–35.

    Article  PubMed  CAS  Google Scholar 

  40. Grace AA, Bunney BS. Electrophysiological properties of midbrain dopamine neurons. In: Bloom F, Kupfer D (eds). Psychopharmacology: The Fourth Generation of Progress. New York: Raven; 1995:163–77.

    Google Scholar 

  41. Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science (New York, NY) 1997;275(5306):1593–9.

    Article  CAS  Google Scholar 

  42. Walters JR, Ruskin DN, Allers KA, Bergstrom DA. Pre- and postsynaptic aspects of dopamine-mediated transmission. Trends Neurosci 2000;23(10 Suppl):S41–7.

    CAS  Google Scholar 

  43. Gerfen CR, Engber TM, Mahan LC, et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 1990;250(4986):1429–32.

    Article  PubMed  CAS  Google Scholar 

  44. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci 1989;12(10):366–75.

    Article  PubMed  CAS  Google Scholar 

  45. Surmeier DJ, Reiner A, Levine MS, Ariano MA. Are neostriatal dopamine receptors co-localized? Trends Neurosci 1993;16(8):299–305.

    Article  PubMed  CAS  Google Scholar 

  46. Bergman H, Wichmann T, DeLong MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 1990;249(4975):1436–8.

    Article  PubMed  CAS  Google Scholar 

  47. Guridi J, Herrero MT, Luquin MR, et al. Subthalamotomy in parkinsonian monkeys. Behavioural and biochemical analysis. Brain 1996;119 (Pt 5):1717–27.

    Article  PubMed  Google Scholar 

  48. Olanow CW, Brin MF, Obeso JA. The role of deep brain stimulation as a surgical treatment for Parkinson's disease. Neurology 2000;55(12 Suppl 6):S60–6.

    PubMed  CAS  Google Scholar 

  49. Waszczak BL, Martin LP, Finlay HE, Zahr N, Stellar JR. Effects of individual and concurrent stimulation of striatal D1 and D2 dopamine receptors on electrophysiological and behavioral output from rat basal ganglia. J Pharmacol Exp Ther 2002;300(3):850–61.

    Article  PubMed  CAS  Google Scholar 

  50. Wang JQ, McGinty JF. The full D1 dopamine receptor agonist SKF-82958 induces neuropeptide mRNA in the normosensitive striatum of rats: regulation of D1/D2 interactions by muscarinic receptors. J Pharmacol Exp Ther 1997;281(2):972–82.

    PubMed  CAS  Google Scholar 

  51. Schindler CW, Carmona GN. Effects of dopamine agonists and antagonists on locomotor activity in male and female rats. Pharmacol Biochem Behav 2002;72(4):857–63.

    Article  PubMed  CAS  Google Scholar 

  52. Krolewski DM, Bishop C, Walker PD. Intrastriatal dopamine D1 receptor agonist-mediated motor behavior is reduced by local neurokinin 1 receptor antagonism. Synapse 2005;57(1):1–7.

    Article  PubMed  CAS  Google Scholar 

  53. Smith ID, Sutton MA, Beninger RJ. Rotational bias in intact rats following intrastriatal injections of dopaminergic drugs. Pharmacol Biochem Behav 1997;58(2):431–41.

    Article  PubMed  CAS  Google Scholar 

  54. Tran AH, Tamura R, Uwano T, Kobayashi T, Katsuki M, Ono T. Dopamine D1 receptors involved in locomotor activity and accumbens neural responses to prediction of reward associated with place. Proc Natl Acad Sci U S A 2005;102(6):2117–22.

    Article  PubMed  CAS  Google Scholar 

  55. Welter M, Vallone D, Samad TA, Meziane H, Usiello A, Borrelli E. Absence of dopamine D2 receptors unmasks an inhibitory control over the brain circuitries activated by cocaine. Proc Natl Acad Sci U S A 2007;104(16):6840–5.

    Article  PubMed  CAS  Google Scholar 

  56. Fornaguera J, Huston JP, Carey RJ, Schwarting RK. Stimulation of D1- or D2-receptors in drug-naive rats with different degrees of unilateral nigro-striatal dopamine lesions. Psychopharmacology (Berl) 1995;119(2):145–54.

    Article  CAS  Google Scholar 

  57. Chait LD, Zacny JP. Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. Psychopharmacology 1992;107(2–3):255–62.

    Article  PubMed  CAS  Google Scholar 

  58. Fernandez-Ruiz J, Lastres-Becker I, Cabranes A, Gonzalez S, Ramos JA. Endocannabinoids and basal ganglia functionality. Prostaglandins Leukot Essent Fatty Acids 2002;66(2–3):257–67.

    Article  PubMed  CAS  Google Scholar 

  59. Navarro M, Fernandez-Ruiz JJ, De Miguel R, Hernandez ML, Cebeira M, Ramos JA. Motor disturbances induced by an acute dose of delta 9-tetrahydrocannabinol: possible involvement of nigrostriatal dopaminergic alterations. Pharmacol Biochem Behav 1993;45(2):291–8.

    Article  PubMed  CAS  Google Scholar 

  60. Prescott WR, Gold LH, Martin BR. Evidence for separate neuronal mechanisms for the discriminative stimulus and catalepsy induced by delta 9-THC in the rat. Psychopharmacology (Berl) 1992;107(1):117–24.

    Article  CAS  Google Scholar 

  61. Lichtman AH, Martin BR. The selective cannabinoid antagonist SR 141716A blocks cannabinoid-induced antinociception in rats. Pharmacol Biochem Behav 1997;57(1–2):7–12.

    Article  PubMed  CAS  Google Scholar 

  62. Anderson LA, Anderson JJ, Chase TN, Walters JR. The cannabinoid agonists WIN 55,212-2 and CP 55,940 attenuate rotational behavior induced by a dopamine D1 but not a D2 agonist in rats with unilateral lesions of the nigrostriatal pathway. Brain Res 1995;691(1–2):106–14.

    Article  PubMed  CAS  Google Scholar 

  63. Chakrabarti A, Ekuta JE, Onaivi ES. Neurobehavioral effects of anandamide and cannabinoid receptor gene expression in mice. Brain Res Bull 1998;45(1):67–74.

    Article  PubMed  CAS  Google Scholar 

  64. Romero J, Garcia L, Cebeira M, Zadrozny D, Fernandez-Ruiz JJ, Ramos JA. The endogenous cannabinoid receptor ligand, anandamide, inhibits the motor behavior: role of nigrostriatal dopaminergic neurons. Life Sci 1995;56(23–24):2033–40.

    Article  PubMed  CAS  Google Scholar 

  65. Smith PB, Compton DR, Welch SP, Razdan RK, Mechoulam R, Martin BR. The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice. J Pharmacol Exp Ther 1994;270(1):219–27.

    PubMed  Google Scholar 

  66. Crawley JN, Corwin RL, Robinson JK, Felder CC, Devane WA, Axelrod J. Anandamide, an endogenous ligand of the cannabinoid receptor, induces hypomotility and hypothermia in vivo in rodents. Pharmacol Biochem Behav 1993;46(4):967–72.

    Article  PubMed  CAS  Google Scholar 

  67. Stein EA, Fuller SA, Edgemond WS, Campbell WB. Physiological and behavioural effects of the endogenous cannabinoid, arachidonylethanolamide (anandamide), in the rat. Br J Pharmacol 1996;119(1):107–14.

    PubMed  CAS  Google Scholar 

  68. Romero J, Garcia-Palomero E, Lin SY, Ramos JA, Makriyannis A, Fernandez-Ruiz JJ. Extrapyramidal effects of methanandamide, an analog of anandamide, the endogenous CB1 receptor ligand. Life Sci 1996;58(15):1249–57.

    Article  PubMed  CAS  Google Scholar 

  69. Beltramo M, de Fonseca FR, Navarro M, et al. Reversal of dopamine D(2) receptor responses by an anandamide transport inhibitor. J Neurosci 2000;20(9):3401–7.

    PubMed  CAS  Google Scholar 

  70. Compton DR, Aceto MD, Lowe J, Martin BR. In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity. J Pharmacol Exp Ther 1996;277(2):586–94.

    PubMed  CAS  Google Scholar 

  71. Cheer JF, Wassum KM, Sombers LA, et al. Phasic dopamine release evoked by abused substances requires cannabinoid receptor activation. J Neurosci 2007;27(4):791–5.

    Article  PubMed  CAS  Google Scholar 

  72. Gerdeman GL, Schechter JB, French ED. Context-specific reversal of cocaine sensitization by the CB(1) cannabinoid receptor antagonist rimonabant. Neuropsychopharmacology 2008;33(11):2747–59.

    Google Scholar 

  73. Ferrer B, Gorriti MA, Palomino A, et al. Cannabinoid CB1 receptor antagonism markedly increases dopamine receptor-mediated stereotypies. Eur J Pharmacol 2007;559(2–3):180–3.

    Article  PubMed  CAS  Google Scholar 

  74. Anderson JJ, Kask AM, Chase TN. Effects of cannabinoid receptor stimulation and blockade on catalepsy produced by dopamine receptor antagonists. Eur J Pharmacol 1996;295(2–3):163–8.

    Article  PubMed  CAS  Google Scholar 

  75. Sanudo-Pena MC, Patrick SL, Patrick RL, Walker JM. Effects of intranigral cannabinoids on rotational behavior in rats: interactions with the dopaminergic system. Neurosci Lett 1996;206(1):21–4.

    Article  PubMed  CAS  Google Scholar 

  76. Sanudo-Pena MC, Force M, Tsou K, Miller AS, Walker JM. Effects of intrastriatal cannabinoids on rotational behavior in rats: interactions with the dopaminergic system. Synapse 1998;30(2):221–6.

    Google Scholar 

  77. El-Banoua F, Caraballo I, Flores JA, Galan-Rodriguez B, Fernandez-Espejo E. Effects on turning of microinjections into basal ganglia of D(1) and D(2) dopamine receptors agonists and the cannabinoid CB(1) antagonist SR141716A in a rat Parkinson's model. Neurobiol Dis 2004;16(2):377–85.

    Article  PubMed  CAS  Google Scholar 

  78. Wu X, French ED. Effects of chronic delta9-tetrahydrocannabinol on rat midbrain dopamine neurons: an electrophysiological assessment. Neuropharmacology 2000;39(3):391–8.

    Article  PubMed  CAS  Google Scholar 

  79. Gonon FG, Buda MJ. Regulation of dopamine release by impulse flow and by autoreceptors as studied by in vivo voltammetry in the rat striatum. Neuroscience 1985;14(3):765–74.

    Article  PubMed  CAS  Google Scholar 

  80. Cheer JF, Wassum KM, Heien ML, Phillips PE, Wightman RM. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci 2004;24(18):4393–400.

    Article  PubMed  CAS  Google Scholar 

  81. Solinas M, Justinova Z, Goldberg SR, Tanda G. Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in rats. J Neurochem 2006;98(2):408–19.

    Article  PubMed  CAS  Google Scholar 

  82. Lupica CR, Riegel AC. Endocannabinoid release from midbrain dopamine neurons: a potential substrate for cannabinoid receptor antagonist treatment of addiction. Neuropharmacology 2005;48(8):1105–16.

    Article  PubMed  CAS  Google Scholar 

  83. Bordet R, Ridray S, Carboni S, Diaz J, Sokoloff P, Schwartz JC. Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa. Proc Natl Acad Sci U S A 1997;94(7):3363–7.

    Article  PubMed  CAS  Google Scholar 

  84. Dewar KM, Soghomonian JJ, Bruno JP, Descarries L, Reader TA. Elevation of dopamine D2 but not D1 receptors in adult rat neostriatum after neonatal 6-hydroxydopamine denervation. Brain Res 1990;536(1–2):287–96.

    Article  PubMed  CAS  Google Scholar 

  85. Zhou QY, Palmiter RD. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 1995;83(7):1197–209.

    Article  PubMed  CAS  Google Scholar 

  86. Robinson S, Smith DM, Mizumori SJ, Palmiter RD. Firing properties of dopamine neurons in freely moving dopamine-deficient mice: effects of dopamine receptor activation and anesthesia. Proc Natl Acad Sci U S A 2004;101(36):13329–34.

    Article  PubMed  CAS  Google Scholar 

  87. Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 1999;2(4):358–63.

    Article  PubMed  CAS  Google Scholar 

  88. Patel S, Hillard CJ. Cannabinoid-induced Fos expression within A10 dopaminergic neurons. Brain Res 2003;963(1–2):15–25.

    Article  PubMed  CAS  Google Scholar 

  89. Pisani A, Fezza F, Galati S, et al. High endogenous cannabinoid levels in the cerebrospinal fluid of untreated Parkinson's disease patients. Ann Neurol 2005;57(5):777–9.

    Article  PubMed  Google Scholar 

  90. Di Marzo V, Hill MP, Bisogno T, Crossman AR, Brotchie JM. Enhanced levels of endogenous cannabinoids in the globus pallidus are associated with a reduction in movement in an animal model of Parkinson's disease. FASEB J 2000;14(10):1432–8.

    Article  PubMed  Google Scholar 

  91. Romero J, Garcia-Palomero E, Castro JG, Garcia-Gil L, Ramos JA, Fernandez-Ruiz JJ. Effects of chronic exposure to delta9-tetrahydrocannabinol on cannabinoid receptor binding and mRNA levels in several rat brain regions. Brain Res Mol Brain Res 1997;46(1–2):100–8.

    Article  PubMed  CAS  Google Scholar 

  92. Appleyard SM, Patterson TA, Jin W, Chavkin C. Agonist-induced phosphorylation of the kappa-opioid receptor. J Neurochemi 1997;69(6):2405–12.

    Article  CAS  Google Scholar 

  93. Dewey WL. Cannabinoid pharmacology. Pharmacol Rev 1986;38(2):151–78.

    PubMed  CAS  Google Scholar 

  94. Sim LJ, Hampson RE, Deadwyler SA, Childers SR. Effects of chronic treatment with delta9-tetrahydrocannabinol on cannabinoid-stimulated [35S]GTPgammaS autoradiography in rat brain. J Neurosci 1996;16(24):8057–66.

    PubMed  CAS  Google Scholar 

  95. Silverdale MA, McGuire S, McInnes A, Crossman AR, Brotchie JM. Striatal cannabinoid CB1 receptor mRNA expression is decreased in the reserpine-treated rat model of Parkinson's disease. Exp Neurol 2001;169(2):400–6.

    Article  PubMed  CAS  Google Scholar 

  96. Hurley MJ, Mash DC, Jenner P. Expression of cannabinoid CB1 receptor mRNA in basal ganglia of normal and parkinsonian human brain. J Neural Transm 2003;110(11):1279–88.

    Article  PubMed  CAS  Google Scholar 

  97. Gonzalez S, Scorticati C, Garcia-Arencibia M, de Miguel R, Ramos JA, Fernandez-Ruiz J. Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat model of Parkinson's disease. Brain Res 2006;1073–1074:209–19.

    Article  PubMed  CAS  Google Scholar 

  98. van der Stelt M, Fox SH, Hill M, et al. A role for endocannabinoids in the generation of parkinsonism and levodopa-induced dyskinesia in MPTP-lesioned non-human primate models of Parkinson's disease. FASEB J 2005;19(9):1140–2.

    PubMed  Google Scholar 

  99. Cao X, Liang L, Hadcock JR, et al. Blockade of cannabinoid type 1 receptors augments the antiparkinsonian action of levodopa without affecting dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys. J Pharmacol Exp Ther 2007;323(1):318–26.

    Article  PubMed  CAS  Google Scholar 

  100. Kreitzer AC, Malenka RC. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models. Nature 2007;445(7128):643–7.

    Article  PubMed  CAS  Google Scholar 

  101. Fernandez-Espejo E, Caraballo I, Rodriguez de Fonseca F, et al. Experimental parkinsonism alters anandamide precursor synthesis, and functional deficits are improved by AM404: a modulator of endocannabinoid function. Neuropsychopharmacology 2004;29(6):1134–42.

    Article  PubMed  CAS  Google Scholar 

  102. de Lago E, Fernandez-Ruiz J, Ortega-Gutierrez S, et al. UCM707, an inhibitor of the anandamide uptake, behaves as a symptom control agent in models of Huntington's disease and multiple sclerosis, but fails to delay/arrest the progression of different motor-related disorders. Eur Neuropsychopharmacol 2006;16(1):7–18.

    Article  PubMed  CAS  Google Scholar 

  103. Garcia-Arencibia M, Gonzalez S, de Lago E, Ramos JA, Mechoulam R, Fernandez-Ruiz J. 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 2007;1134(1):162–70.

    Google Scholar 

  104. Adermark L, Lovinger DM. Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step. Proc Natl Acad Sci U S A 2007;104(51):20564–9.

    Article  PubMed  CAS  Google Scholar 

  105. Ronesi J, Gerdeman GL, Lovinger DM. Disruption of endocannabinoid release and striatal long-term depression by postsynaptic blockade of endocannabinoid membrane transport. J Neurosci 2004;24(7):1673–9.

    Article  PubMed  CAS  Google Scholar 

  106. Straiker A, Mackie K. Depolarization-induced suppression of excitation in murine autaptic hippocampal neurons. J Physiol 2005;569(Pt 2):501–17.

    Article  PubMed  CAS  Google Scholar 

  107. Chen Y, Buck J. Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism. J Pharmacol Exp Ther 2000;293(3):807–12.

    PubMed  CAS  Google Scholar 

  108. Marsicano G, Moosmann B, Hermann H, Lutz B, Behl C. Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. J Neurochem 2002;80(3):448–56.

    Article  PubMed  CAS  Google Scholar 

  109. Lastres-Becker I, Molina-Holgado F, Ramos JA, Mechoulam R, Fernandez-Ruiz J. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease. Neurobiol Dis 2005;19(1–2):96–107.

    Article  PubMed  CAS  Google Scholar 

  110. Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A 1998;95(14):8268–73.

    Article  PubMed  CAS  Google Scholar 

  111. Ferrer B, Asbrock N, Kathuria S, Piomelli D, Giuffrida A. Effects of levodopa on endocannabinoid levels in rat basal ganglia: implications for the treatment of levodopa-induced dyskinesias. Eur J Neurosci 2003;18(6):1607–14.

    Article  PubMed  Google Scholar 

  112. Fox SH, Lang AE, Brotchie JM. Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure. Mov Disord 2006;21(10):1578–94.

    Article  PubMed  Google Scholar 

  113. Meschler JP, Howlett AC, Madras BK. 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) 2001;156(1):79–85.

    Article  CAS  Google Scholar 

  114. Gilgun-Sherki Y, Melamed E, Mechoulam R, Offen D. The CB1 cannabinoid receptor agonist, HU-210, reduces levodopa-induced rotations in 6-hydroxydopamine-lesioned rats. Pharmacol Toxicol 2003;93(2):66–70.

    Article  PubMed  CAS  Google Scholar 

  115. Fernandez-Espejo E, Caraballo I, de Fonseca FR, et al. Cannabinoid CB1 antagonists possess antiparkinsonian efficacy only in rats with very severe nigral lesion in experimental parkinsonism. Neurobiol Dis 2005;18(3):591–601.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA

    Joseph F. Cheer

Authors
  1. Sarah E. McCallum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph F. Cheer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph F. Cheer .

Editor information

Editors and Affiliations

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2009 Humana Press, a part of Springer Science+Business Media, LLC

    About this chapter

    Cite this chapter

    McCallum, S.E., Cheer, J.F. (2009). Dopamine–Endocannabinoid Interactions in Parkinson’s Disease. In: Tseng, KY. (eds) Cortico-Subcortical Dynamics in Parkinson's Disease. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-60327-252-0_12

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation