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The Neurobiology of the Substantia Nigra Pars Compacta: from Motor to Sleep Regulation

  • Marcelo M. S. LimaEmail author
  • Angela B. B. Reksidler
  • Maria A. B. F. Vital
Chapter
Part of the Journal of Neural Transmission. Supplementa book series (NEURALTRANS, volume 73)

Abstract

Clinical characteristics of Parkinson´s disease (PD) are the result of the degeneration of the neurons of the substantia nigra pars compacta (SNpc). Several mechanisms are implicated in the degeneration of nigrostriatal neurons such as oxidative stress, mitochondrial dysfunction, protein misfolding, disturbances of dopamine (DA) metabolism and transport, neuroinflammation, and necrosis/apoptosis. The literature widely explores the neurotoxic models elicited by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA). Because of the models, it is known that basal ganglia, particularly substantia nigra, have been related to a diversity of functions, from motor to sleep regulation. Nevertheless, a current debate concerning the role of DA on the sleep–wake cycle is in progress. In summary, it is suggested that the dopaminergic system is implicated in the physiology of sleep, with particular regard to the influence of the SNpc neurons. The understanding of the functioning and connectivity of the SNpc neurons has become fundamental to discovering the neurobiology of these neurons.

Keywords

6-OHDA Motor MPTP Sleep Substantia nigra pars compacta 

Notes

Acknowledgments

This work was supported by CAPES (PRODOC-Farmacologia UFSC to MMSL). MABFV is a recipient of CNPq fellowship.

References

  1. Andrade LA, Lima JG, Tufik S, Bertolucci PH, Carlini EA (1987) Rem sleep deprivation in an experimental model of Parkinson’s disease. Arq Neuropsiquiatr 45(3):217–223PubMedGoogle Scholar
  2. Arnulf I (2006) Sleep and wakefulness disturbances in Parkinson’s disease. J Neural Transm Suppl 70:357–360PubMedGoogle Scholar
  3. Arnulf I, Konofal E, Merino-Andreu M, Houeto JL, Mesnage V, Welter ML, Lacomblez L, Golmard JL, Derenne JP, Agid Y (2002) Parkinson’s disease and sleepiness: an integral part of PD. Neurology 58(7):1019–1024PubMedGoogle Scholar
  4. Asanuma M, Miyazaki I (2006) Nonsteroidal anti-inflammatory drugs in Parkinson’s disease: possible involvement of quinone formation. Expert Rev Neurother 6(9):1313–1325PubMedGoogle Scholar
  5. Barbeau A et al. (1961) Les catecholamines dans la maladie de Parkinson. In Georg (ed) CMonoamines et Syste`me Nerveux Central. Geneva, pp. 247-262Google Scholar
  6. Barnham JK, Masters AB, Bush A (2004) Neurodegenerative disease and oxidative stress. Nat Rev Drug Discov 3:205–214PubMedGoogle Scholar
  7. Berman SB, Hastings TG (1999) Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson’s disease. J Neurochem 73(3):1127–1137PubMedGoogle Scholar
  8. Birkmayer W, Hornykiewicz O (1961) Der L-3, 4-dioxyphenylalanin (L-DOPA)-effect bei der Parkinson-akinese. Klin Wschr 73:787–788Google Scholar
  9. Bové J, Prou D, Perier C, Przedborski S (2005) Toxin-induced models of Parkinson´s disease. The Journal of the American Society for Experimental NeuroTherapeutics 2:484–494Google Scholar
  10. Braga R, Kouzmine I, Canteras NS, Da Cunha C (2005) Lesion of the substantia nigra, pars compacta impairs delayed alternation in a Y-maze in rats. Exp Neurol 192(1):134–141PubMedGoogle Scholar
  11. Carlini EA (1983) REM sleep deprivation and dopamine in the CNS. Rev Pure Appl Pharmacol Sci 4(1):1–25PubMedGoogle Scholar
  12. Carlini EA, Lindsey CJ, Tufik S (1977) Cannabis, catecholamines, rapid eye movement sleep and aggressive behaviour. Br J Pharmacol 61(3):371–379PubMedGoogle Scholar
  13. Chen H, Zhang SM, Hernan MA, Schwarzschild MA, Willett WC, Colditz GA, Speizer FE, Ascherio A (2003) Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol 60(8):1059–1064PubMedGoogle Scholar
  14. Chiba K, Trevor A, CJ N (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem Biophys Res Commun 120:574–578PubMedGoogle Scholar
  15. Cotzias GC (1968) L-DOPA for Parkinsonism. N Engl J Med 278:630PubMedGoogle Scholar
  16. Cui K, Luo X, Xu K, Vem Murthy MR (2004) Role of oxidative stress in neurodegeneration: recent developments in assay methods for oxidative stress and nutraceutical antioxidants. Prog Neuropsychopharmacol Biol Psychiatry 28:771–799PubMedGoogle Scholar
  17. Da Cunha C, Gevaerd MS, Vital MA, Miyoshi E, Andreatini R, Silveira R, Takahashi RN, Canteras NS (2001) Memory disruption in rats with nigral lesions induced by MPTP: a model for early Parkinson’s disease amnesia. Behav Brain Res 124(1):9–18PubMedGoogle Scholar
  18. Dahan L, Astier B, Vautrelle N, Urbain N, Kocsis B, Chouvet G (2007) Prominent Burst Firing of Dopaminergic Neurons in the Ventral Tegmental Area during Paradoxical Sleep. Neuropsychopharmacology 32(6):1232–1241PubMedGoogle Scholar
  19. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909PubMedGoogle Scholar
  20. De Cock VC, Vidailhet M, Leu S, Texeira A, Apartis E, Elbaz A, Roze E, Willer JC, Derenne JP, Agid Y, Arnulf I (2007) Restoration of normal motor control in Parkinson’s disease during REM sleep. Brain 130(Pt 2):450–456PubMedGoogle Scholar
  21. Deumens R, Blokland A, Prickaerts J (2002) Modeling Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303–307PubMedGoogle Scholar
  22. Di Matteo V, Pierucci M, Di Giovanni G, Di Santo A, Poggi A, Benigno A, Esposito E (2006) Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study. Brain Res 1095(1):167–177PubMedGoogle Scholar
  23. Dzirasa K, Ribeiro S, Costa R, Santos LM, Lin SC, Grosmark A, Sotnikova TD, Gainetdinov RR, Caron MG, Nicolelis MA (2006) Dopaminergic control of sleep-wake states. J Neurosci 26(41):10577–10589PubMedGoogle Scholar
  24. Ehringer H, Hornykiewicz O (1960) Verteilung von noradrenalin und dopamine (3-hydroxtyramin) im gehirn des menschen und ihr verhalten bei erkankungen des extrapyamidalen systems. Klin Wschr 38:1236–1239PubMedGoogle Scholar
  25. Esposito E, Di Matteo V, Benigno A, Pierucci M, Crescimanno G, Di Giovanni G (2007) Non-steroidal anti-inflammatory drugs in Parkinson’s disease. Exp Neurol 205(2):295–312PubMedGoogle Scholar
  26. Faull RL, Laverty R (1969) Changes in dopamine levels in the corpus striatum following lesions in the substantia nigra. Exp Neurol 23:332–340PubMedGoogle Scholar
  27. Ferger B, Teismann P, Earl CD, Kuschinsky K, Oertel WH (1999) Salicylate protects against MPTP-induced impairments in dopaminergic neurotransmission at the striatal and nigral level in mice. Naunyn Schmiedebergs Arch Pharmacol 360(3):256–261PubMedGoogle Scholar
  28. Ferro MM, Bellissimo MI, Anselmo-Franci JA, Angellucci ME, Canteras NS, Da Cunha C (2005) Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson’s disease: histological, neurochemical, motor and memory alterations. J Neurosci Methods 148(1):78–87PubMedGoogle Scholar
  29. Franco J, Prediger RD, Pandolfo P, Takahashi RN, Farina M, Dafre AL (2007) Antioxidant responses and lipid peroxidation following intranasal 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) administration in rats: increased susceptibility of olfactory bulb. Life Sci 80(20):1906–1914PubMedGoogle Scholar
  30. Gainetdinov RR, Fumagalli F, Jones SR, Caron MG (1997) Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter. J Neurochem 69:1322–1325PubMedGoogle Scholar
  31. Gevaerd MS, Miyoshi E, Silveira R, Canteras NS, Takahashi RN, Da Cunha C (2001) L-Dopa restores striatal dopamine level but fails to reverse MPTP-induced memory deficits in rats. Int J Neuropsychopharmacol 4(4):361–370PubMedGoogle Scholar
  32. Hastings TG (1995) Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 64(2):919–924PubMedGoogle Scholar
  33. Heikkila RE, Hess A, Duvoisin RC (1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine in mice. Science 224:1451–1453PubMedGoogle Scholar
  34. Hogl B, Rothdach A, Wetter TC, Trenkwalder C (2003) The effect of cabergoline on sleep, periodic leg movements in sleep, and early morning motor function in patients with Parkinson’s disease. Neuropsychopharmacology 28(10):1866–1870PubMedGoogle Scholar
  35. Iversen SD, Iversen LL (2007) Dopamine: 50 years in perspective. Trends Neurosci 30(5):188–193PubMedGoogle Scholar
  36. Jones BE (2003) Arousal systems. Front Biosci 8:s438–s451PubMedGoogle Scholar
  37. Kebabian JW, Calne BD (1979) Multiple receptors for dopamine. Nature 277:93–96PubMedGoogle Scholar
  38. Kebabian JW, Petzold GL, Greengard P (1972) Dopamine-sensitive anenylate cyclase in caudate nucleus of rat brain and its similarity to the dopamine receptor. Proc Natl Acad Sci USA 69:2145–2149PubMedGoogle Scholar
  39. Laloux C, Derambure P, Kreisler A, Houdayer E, Bruezière S, Bordet R, Destée A, Monaca C (2008) MPTP-treated mice: long-lasting loss of nigral TH-ir neurons but not paradoxical sleep alterations. Exp Brain Res 186:635–642PubMedGoogle Scholar
  40. Lane E, Dunnett S (2007) Animal models of Parkinson´s disease and L-dopa induced dyskinesia: How close are we to the clinic? Psychopharmacology (Berl) 199:303–312Google Scholar
  41. Lang AE, Lozano AM (1998) Parkinson´s disease. First of two parts. N Engl J Med 339:1044–1053PubMedGoogle Scholar
  42. Langston JW, Ballard PA Jr (1983) Parkinson’s disease in a chemist working with 1-methyl-4-phenyl-1, 2, 5, 6-tetrahydropyridine. N Engl J Med 309(5):310PubMedGoogle Scholar
  43. Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219(4587):979–980PubMedGoogle Scholar
  44. Larsen JP, Tandberg E (2001) Sleep disorders in patients with Parkinson’s disease: epidemiology and management. CNS Drugs 15(4):267–275PubMedGoogle Scholar
  45. Lee CS, Sauer H, Bjorklund A (1996) Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by intrastriatal 6- hydroxydopamine in the rat. Neuroscience 72: 641–653PubMedGoogle Scholar
  46. Lelkes Z, Stenberg D, Porkka-Heiskanen T (1991) Effect of MPTP on sleep in rats. Sleep Res 20A:154Google Scholar
  47. Liang LP, Patel M (2004) Iron-sulfur enzyme mediated mitochondrial superoxide toxicity in experimental Parkinson’s disease. J Neurochem 90(5):1076–1084PubMedGoogle Scholar
  48. Lima MMS, Braga Reksidler A, Marques Zanata S, Bueno Machado H, Tufik S, Vital MA (2006) Different parkinsonism models produce a time-dependent induction of COX-2 in the substantia nigra of rats. Brain Res 1101(1):117–125Google Scholar
  49. Lima MMS, Andersen ML, Reksidler AB, Vital MABF, Tufik S (2007) The role of the substantia nigra pars compacta in regulating sleep patterns in rats. PLoS ONE 2:e513PubMedGoogle Scholar
  50. Lima MM, Andersen ML, Reksidler AB, Silva A, Zager A, Zanata SM, Vital MA, Tufik S (2008a) Blockage of dopaminergic D(2) receptors produces decrease of REM but not of slow wave sleep in rats after REM sleep deprivation. Behav Brain Res 188(2):406–411PubMedGoogle Scholar
  51. Lima MMS, Reksidler AB, Vital MABF (2008b) The dopaminergic dilema: Sleep or wake? implications in Parkinson´s disease. Biosci Hypothesis 1:9–13Google Scholar
  52. Lu J, Jhou TC, Saper CB (2006) Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J Neurosci 26(1):193–202PubMedGoogle Scholar
  53. Marsden CA (2006) Dopamine: the rewarding years. Br J Pharmacol 147(Suppl 1):S136–S144PubMedGoogle Scholar
  54. McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8(4):302–330PubMedGoogle Scholar
  55. Mena-Segovia J, Bolam JP, Magill PJ (2003) Pedunculopontine nucleus and basal ganglia: distant relatives or part of the same family? Trends Neurosci 27:585–588Google Scholar
  56. Meredith GE, Totterdell S, Potashkin JA, Surmeier J (2008) Modeling PD pathogenesis in mice: Advantages of a chronic MPTP protocol. Parkinsonism Relat Disord 14:S112–S115PubMedGoogle Scholar
  57. Miyawaki E, Lyons K, Pahwa R, Troster AI, Hubble J, Smith D, Busenbark K, McGuire D, Michalek D, Koller WC (1997) Motor complications of chronic levodopa therapy in Parkinson’s disease. Clin Neuropharmacol 20(6):523–530PubMedGoogle Scholar
  58. Miyoshi E, Wietzikoski S, Camplessei M, Silveira R, Takahashi RN, Da Cunha C (2002) Impaired learning in a spatial working memory version and in a cued version of the water maze in rats with MPTP-induced mesencephalic dopaminergic lesions. Brain Res Bull 58(1):41–47PubMedGoogle Scholar
  59. Monti JM (1982) Catecholamines and the sleep-wake cycle. I. EEG and behavioral arousal. Life Sci 30(14):1145–1157PubMedGoogle Scholar
  60. Monti JM, Monti D (2007) The involvement of dopamine in the modulation of sleep and waking. Sleep Med Rev 11(2):113–133PubMedGoogle Scholar
  61. Nunes GP, Tufik S, Nobrega JN (1994) Autoradiographic analysis of D1 and D2 dopaminergic receptors in rat brain after paradoxical sleep deprivation. Brain Res Bull 34(5):453–456Google Scholar
  62. Pace-Schott EF, Hobson JA (2002) The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 3(8):591–605PubMedGoogle Scholar
  63. Perry JC, Da Cunha C, Anselmo-Franci J, Andreatini R, Miyoshi E, Tufik S, Vital MA (2004) Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats. Eur J Pharmacol 484(2–3):225–233PubMedGoogle Scholar
  64. Porkka-Heiskanen T, Tuomisto L, Ylinen M, Stenberg D (1994) The effect of REM sleep deprivation on histamine concentrations in different brain areas. Life Sci 54(22):1719–1726PubMedGoogle Scholar
  65. Portas CM, Bjorvatn B, Ursin R (2000) Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies. Prog Neurobiol 60(1):13–35PubMedGoogle Scholar
  66. Porter CC, Totaro JA, Stone CA (1963) Effect of 6-hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. J Pharmacol Exp Ther 140:308–316PubMedGoogle Scholar
  67. Prediger RD, Batista LC, Medeiros R, Pandolfo P, Florio JC, Takahashi RN (2006) The risk is in the air: Intranasal administration of MPTP to rats reproducing clinical features of Parkinson’s disease. Exp Neurol 202(2):391–403PubMedGoogle Scholar
  68. Przedborski S (2005) Pathogenesis of nigral cell death in Parkinson’s disease. Parkinsonism Relat Disord 11(Suppl 1):S3–S7PubMedGoogle Scholar
  69. Przedborski S, Tieu K, Perier C, Vila M (2004) MPTP as a mitochondrial neurotoxic model of Parkinson’s disease. J Bioenerg Biomembr 36(4):375–379PubMedGoogle Scholar
  70. Pulst S-M (2003) Genetics of Movement disorders. Academic Press San Diego, California USAGoogle Scholar
  71. Pungor K, Papp M, Kekesi K, Juhasz G (1990) A novel effect of MPTP: the selective suppression of paradoxical sleep in cats. Brain Res 525(2):310–314PubMedGoogle Scholar
  72. Reavill C, Jenner P, Marsden CD (1980) Metabolite involvement in bromocriptine-induced circling behaviour in rodents. J Pharm Pharmacol 32(4):278–284PubMedGoogle Scholar
  73. Reksidler AB, Lima MMS, Zanata SM, Machado HB, da Cunha C, Andreatini R, Tufik S, Vital MABF (2007) The COX-2 inhibitor parecoxib produces neuroprotective effects in MPTP-lesioned rats. Eur J Pharmacol 560(2–3):163–175PubMedGoogle Scholar
  74. Reksidler AB, Lima MMS, Dombrowski P, Andersen ML, Zanata SM, Andreatini R, Tufik S, Vital MABF (2008) Repeated intranigral MPTP administration: A new protocol of prolonged locomotor impairment mimicking Parkinson’s disease. J Neurosci Methods 167(2):268–277PubMedGoogle Scholar
  75. Reksidler AB, Lima MMS, Dombrowski P, Barnabé GF, Andersen ML, Tufik S, Vital MABF (2009) Distinct effects of intranigral L-DOPA infusion in the MPTP rat model of Parkinson’s disease. In: G. Di Giovanni, V. Di Matteo, E. Esposito (ed) Birth, life and death of dopaminergic neurons in the Substantia Nigra. Journal of Neural Transmission, Vol 73, Springer HeidelbergGoogle Scholar
  76. Rollema H, Kuhr WG, Kranenborg G, De Vries J, Van den Berg C (1988) MPP+-induced efflux of dopamine and lactate from rat striatum have similar time courses as shown by in vivo brain dialysis. J Pharmacol Exp Ther 245(3):858–866PubMedGoogle Scholar
  77. Sairam K, Saravanan KS, Banerjee R, Mohanakumar KP (2003) Non-steroidal anti-inflammatory drug sodium salicylate, but not diclofenac or celecoxib, protects against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats. Brain Res 966(2):245–252PubMedGoogle Scholar
  78. Schapira AHV, Bezard E, Brotchie J (2006) Novel pharmacological targets for the treatment of Parkinson’s disease. Nat Rev Drug Discov 5:845–854PubMedGoogle Scholar
  79. Sedelis M, Schwarting RKW, Huston JP (2001) Behavioral phenotyping of the MPTP mouse model of Parkinson’s disease. Behav Brain Res 125:109–125PubMedGoogle Scholar
  80. Seeman P, Lee T, Chau-Wong M, Wong K (1976) Antipsychotic drug doses and neuroleptics/dopamine receptors. Nature 261: 717–719PubMedGoogle Scholar
  81. Serra PA, Sciola L, Delogu MR, Spano A, Monaco G, Miele E (2002) The neurotoxin MPTP induces apoptosis in mouse nigro-striatal glia Relevance to nigral neuronal death and striatal neurochemical changes. J Biol Chem 277:34451–34461PubMedGoogle Scholar
  82. Siegel JM (2004) Hypocretin (orexin): role in normal behavior and neuropathology. Annu Rev Psychol 55:125–148PubMedGoogle Scholar
  83. Simola N, Morelli M, Carta AR (2007) The 6-hydroxydopamine model of Parkinson’s disease. Neurotox Res 11(3–4):151–167PubMedGoogle Scholar
  84. Sonsalla PK, Heikkila RE (1986) The influence of dose and dosing interval on MPTP-induced dopaminergic neurotoxicity in mice. Eur Eur. J. Pharmacol 129:339–345PubMedGoogle Scholar
  85. Speciale SG (2002) Insights into parkinsonian neurodegeneration. Neurotoxicol Teratol 24:607–620PubMedGoogle Scholar
  86. Speciale SG, Liang CL, Sonsalla PK, Edwards RH, German DC (1998) The neurotoxin 1-methyl-4-phenylpyridinium is sequestered within neurons that contain the vesicular monoamine transporter. Neuroscience 84(4):1177–1185PubMedGoogle Scholar
  87. Steininger TL, Alam MN, Gong H, Szymusiak R, McGinty D (1999) Sleep-waking discharge of neurons in the posterior lateral hypothalamus of the albino rat. Brain Res 840(1–2):138–147PubMedGoogle Scholar
  88. Steriade M, Amzica F, Nunez A (1993) Cholinergic and noradrenergic modulation of the slow (approximately 0.3 Hz) oscillation in neocortical cells. J Neurophysiol 70(4):1385–1400PubMedGoogle Scholar
  89. Sundström E, Strömberg I, Tsutsumi T, Olson I, Josson G (1987) Studies on the effect of 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice. Comparison with three other strains of mice. Brain Res 405: 26–38PubMedGoogle Scholar
  90. Tandberg E, Larsen JP, Karlsen K (1998) A community-based study of sleep disorders in patients with Parkinson’s disease. Mov Disord 13(6):895–899PubMedGoogle Scholar
  91. Tatton NA, Kish SJ (1997) In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining. Neuroscience 77: 1037–1048PubMedGoogle Scholar
  92. Teismann P, Ferger B (2001) Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson’s disease. Synapse 39(2):167–174PubMedGoogle Scholar
  93. Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, Vila M, Jackson-Lewis V, Przedborski S (2003a) Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci USA 100(9):5473–5478PubMedGoogle Scholar
  94. Teismann P, Vila M, Choi DK, Tieu K, Wu DC, Jackson-Lewis V, Przedborski S (2003b) COX-2 and neurodegeneration in Parkinson’s disease. Ann NY Acad Sci 991:272–277PubMedGoogle Scholar
  95. Thobois S, Delamarre-Damier F, Derkinderen P (2005) Treatment of motor dysfunction in Parkinson’s disease: an overview. Clin Neurol Neurosurg 107(4):269–281PubMedGoogle Scholar
  96. Thomson F et al (2001) Parkinson’s disease: treatment. Pharm J 267:600–613Google Scholar
  97. Truong DD, Bhidayasiri R, Wolters E (2008) Management of non-motor symptoms in advanced Parkinson disease. J Neurol Sci 266(1–2):216–228PubMedGoogle Scholar
  98. Tufik S (1981a) Changes of response to dopaminergic drugs in rats submitted to REM-sleep deprivation. Psychopharmacology (Berl) 72(3):257–260Google Scholar
  99. Tufik S (1981b) Increased responsiveness to apomorphine after REM sleep deprivation: supersensitivity of dopamine receptors or increase in dopamine turnover? J Pharm Pharmacol 33(11):732–738PubMedGoogle Scholar
  100. Tufik S, Lindsey CJ, Carlini EA (1978) Does REM sleep deprivation induce a supersensitivity of dopaminergic receptors in the rat brain? Pharmacology 16(2):98–105PubMedGoogle Scholar
  101. Ungerstedt U (1968) 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5:107–110PubMedGoogle Scholar
  102. Ungerstedt U (1971a) Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:95–122PubMedGoogle Scholar
  103. Ungerstedt U (1971b) Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:69–93PubMedGoogle Scholar
  104. Whitton PS (2007) Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol 150(8):963–976PubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien Printed in Germany 2009

Authors and Affiliations

  • Marcelo M. S. Lima
    • 1
    Email author
  • Angela B. B. Reksidler
    • 2
  • Maria A. B. F. Vital
    • 2
  1. 1.Departamento de Farmacologia, Centro de Ciências BiológicasUniversidade Federal de Santa Catarina, Campus Universitário, TrindadeFlorianópolisBrazil
  2. 2.Departamento de FarmacologiaUniversidade Federal do ParaáCuritibaBrazil

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