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Dopamine and Glutamate in Psychiatric Disorders pp 523–535Cite as

Dopamine and Glutamate in Motor and Cognitive Symptoms of Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is characterized by motor and cognitive deficits. The main motor symptoms of PD are on the one hand hypokinetic signs, such as bradykinesia, akinesia, rigidity, and loss of postural reflexes, and on the other hand hyperkinetic signs, such as tremor, (see Chapter 21; ref. 1). Cognitive deficits in nondemented PD patients comprise deficits in sensitivity to reward (2), deficits in procedural and habit learning (3), and deficits in switching arbitrarily from one behavioral activity to another, possibly owing to a deficit in attentional set shifting (4). It has even been argued that PD patients are deficient in so-called executive functions of human mind (5,6). “Executive function is a neuropsychological construct that has been used to capture the highest order of cognitive abilities,” e.g., flexibility of thought in the generation of solutions to novel problems (7,8). The reason why the cognitive aspects are not well perceived may be that in humans, the cognitive functions in PD are mainly unconscious; they are thus not experienced and cannot be explicitely communicated. Another reason that renders analysis of PD symptoms so difficult is that the diseased human brain is able to use (cortical) loops to bypass or compensate for basal ganglia (BG) dysfunctions, however, with the disadvantage of a loss of parallel processing and reduced velocity.

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References

  1. Bergmann H, Deuschl G. Pathophysiology of Parkinson’s disease: from clinical neurology to basic neuroscience and back. Mov Dis 2002; 17(Suppl 3):S28–S40.

    Article  Google Scholar 

  2. Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B. Motivation, reward, and Parkinson’s disease: influence of dopatherapy. Neuropsychologia 2002; 40:2257–2267.

    Article  CAS  PubMed  Google Scholar 

  3. Knowlton BJ, Mangels JA, Squire LR. A neostriatal habit learning system in humans. Science 1996; 273:1399–1402.

    Article  CAS  PubMed  Google Scholar 

  4. Cools AR, Van den Bercken JHL, Horstink MWI, Van Spaendonck KPM. Cognitive and motor shifting aptitude disorder in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1984; 47:443–453.

    Article  CAS  PubMed  Google Scholar 

  5. Litvan I, Mohr E, Williams J, Gomez C, Chase TN. Differential memory and executive functions in demented patients with Parkinson’s and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1991; 54:25–29.

    Article  CAS  PubMed  Google Scholar 

  6. Dubois B, Pillon B. Cognitive deficits in Parkinson’s disease. J Neurol 1997; 244:2–8.

    Article  CAS  PubMed  Google Scholar 

  7. Brown LL, Schneider JS, Lidsky TI. Sensory and cognitive functions of the basal ganglia. Curr Opin Neurobiol 1997; 7:157–163.

    Article  CAS  PubMed  Google Scholar 

  8. Lieberman MD. Intuition: a social cognitive neuroscience approach. Psychol Bull 2000; 126:109–137.

    Article  CAS  PubMed  Google Scholar 

  9. Schultz W. Multiple reward signals in the brain. Nat Rev Neurosci 2000; 1:199–207.

    Article  CAS  PubMed  Google Scholar 

  10. Beninger RJ. The role of dopamine in locomotor activity and learning. Brain Res Rev 1983; 6:173–196.

    Article  CAS  Google Scholar 

  11. Schultz W, Tremblay L, Hollerman JR. Changes in behavior-related neuronal activity in the striatum during learning. Trends Neurosci 2003; 26(6):321–328.

    Article  CAS  PubMed  Google Scholar 

  12. Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science 1997; 275:1593–1599.

    Article  CAS  PubMed  Google Scholar 

  13. Hassler R. Striatal control of locomotion, intentional actions and of integrating and perceptive acitivty. J Neurol Sci 1978; 36:187–224.

    Article  CAS  PubMed  Google Scholar 

  14. Hauber W. Involvement of basal ganglia transmitter systems in movement initiation. Prog Neurobiol 1998; 56:507–540.

    Article  CAS  PubMed  Google Scholar 

  15. Schmidt WJ. Intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine. Psychopharmacology 1986; 90:123–130.

    Article  CAS  PubMed  Google Scholar 

  16. Dick JPR, Rothwell JC, Day BL, et al. The bereitschaftspotential is abnormal in Parkinson’s disease. Brain 1989; 112:233.

    Article  PubMed  Google Scholar 

  17. Alam M, Schmidt WJ. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 2002; 136:317–324.

    Article  CAS  PubMed  Google Scholar 

  18. Wegener S, Schmidt WJ, Ehret G. Haloperidol-and apomorphine-induced changes in pup searching behaviour of house mice. Psychopharmacology 1988; 95:271–275.

    Article  CAS  PubMed  Google Scholar 

  19. Schmidt WJ. L-dopa and apomorphine disrupt long-but not short-behavioural chains. Physiol Behav 1984; 33:671–680.

    Article  CAS  PubMed  Google Scholar 

  20. Piemont ME, Xavier GF. Improvement of performance in daily life activities in patients with parkinson’s disease by using declarative memory-guided sequences of instructions for sub-components of the movements. Society for Neuroscience, 30th annual meeting, New Orleans, LA, 2000: 278.20.

    Google Scholar 

  21. Lyon M, Robbins T. The action of central nervous system stimulant drugs: a general theory concerning amphetamine effects. Curr Develop Psychopharmacol 1975; 2:80–163.

    Google Scholar 

  22. Cools AR. Role of the neostriatal dopaminergic activity in sequencing and selecting behavioural strategies: facilitation of processes involved in selecting the best strategy in a stressful situation. Behav Brain Res 1980; 1:361–378.

    Article  CAS  PubMed  Google Scholar 

  23. Schmidt WJ. Involvement of dopaminergic neurotransmission in the control of goaldirected movements. Psychopharmacology 1983; 80:360–364.

    Article  CAS  PubMed  Google Scholar 

  24. Hayes AE, Davidson MC, Keele SW, Rafal RD. Toward a functional analysis of the basal ganglia. J Cogn Neurosci 1998; 10(2):178–198.

    Article  CAS  PubMed  Google Scholar 

  25. Morris RG, Downes JJ, Sahakian BJ, Evenden JL, Heald A, Robbins TW. Planning and spatial working memory in Parkinson’s disease. J Neurol Neurosurg Psychiatry1988; 51:757–766.

    Article  CAS  PubMed  Google Scholar 

  26. Kunig G, Leenders KL, Martin-Solch C, Missimer J, Magyar S, Schultz W. Reduced reward processing in the brains of Parkinsonian patients. Neuroreport 2000; 11(17):3681–3687.

    CAS  PubMed  Google Scholar 

  27. Swainson R, Rogers RD, Sahakian BJ, Summers BA, Polkey CE, Robbins TW. Probabilistic learning and reversal deficits in patients with Parkinson’s disease or frontal or temporal lobe lesions: possible adverse effects of dopaminergic medication. Neuropsychologia 2000; 38(5):596–612.

    Article  CAS  PubMed  Google Scholar 

  28. Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B. Motivation, reward, and Parkinson’s disease: influence of dopatherapy. Neuropsychologia 2002; 40(13):2257–2267.

    Article  CAS  PubMed  Google Scholar 

  29. Persico AM, Reich S, Henningfield JE, Kuhar MJ, Uhl GR. Parkinsonian patients report blunted subjective effects of methylphenidate. Exp Clin Psychopharmacol 1998; 6(1):54–63.

    Article  CAS  PubMed  Google Scholar 

  30. White NM. Reward or reinforcement: what’s the difference? Neurosci Biobehav Rev 1989; 13:181–186.

    Article  CAS  PubMed  Google Scholar 

  31. Wise RA. Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 1982; 5:39–87.

    Article  Google Scholar 

  32. Gold JI. Linking reward expectation to behavior in the basal ganglia. Trends Neurosci 2003; 26(1):12–14.

    Article  CAS  PubMed  Google Scholar 

  33. White NM, McDonald RJ. Multiple parallel memory systems in the brain of the rat. Neurobiol Learn Mem 2002; 77:125–184.

    Article  PubMed  Google Scholar 

  34. Packard MG, Knowlton BJ. Learning and memory functions of the basal ganglia. Annu Rev Neurosci 2002; 25:563–593.

    Article  CAS  PubMed  Google Scholar 

  35. Benedetti F, Pollo A. The pharmacology of placebos. Int J Pain Med Pall Care 2001; 1(2):42–48.

    Google Scholar 

  36. Goetz CG, Leurgans S, Raman R, Stebbins GT. Objective changes in motor function during placebo treatment in PD. Neurology 2000; 54(1):710–714.

    CAS  PubMed  Google Scholar 

  37. De la Fuente-Fernández R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ. Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease. Science 2001; 293:1164–1166.

    Article  PubMed  Google Scholar 

  38. Hillegaart V, Ahlenius S, Magnusson O, Fowler CJ. Repeated testing of rats markedly enhances the duration of effects induced by haloperidol on treadmill locomotion, catalepsy, and a conditioned avoidance response. Pharmacol Biochem Behav 1987; 27:159–164.

    Article  CAS  PubMed  Google Scholar 

  39. Klein A, Schmidt WJ. Catalepsy intensifies context-dependently irrespective of whether it is induced by intermittent or chronic dopamine deficiency. Behav Pharmacol 2003; 14:49–53.

    CAS  PubMed  Google Scholar 

  40. Amtage J, Schmidt WJ. Context-dependent catalepsy-intensification is due to classical conditioning and sensitisation. Behav Pharmacol 2003; 14:563–547.

    Article  CAS  PubMed  Google Scholar 

  41. Tzschentke TM, Schmidt WJ. Glutamatergic mechanisms in addiction. Mol Psychiatry 2003; 8(4):373–382.

    Article  CAS  PubMed  Google Scholar 

  42. Potegal M. Role of the caudate nucleus in spatial orientation of rats. J Comp Physiol Psychol 1969; 69(4):756–764.

    Article  CAS  PubMed  Google Scholar 

  43. Cook D, Kesner RP. Caudate nucleus and memory for egocentric localization. Behav Neural Biol 1988; 49:332–343.

    Article  CAS  PubMed  Google Scholar 

  44. Adamovich SV, Berkinblit MB, Hening W, Sage J, Poizner H. The interaction of visual and proprioceptive inputs in pointing to actual and remembered targets in Parkinson’s disease. Neuroscience 2001; 104(4):1027–1041.

    Article  CAS  PubMed  Google Scholar 

  45. Lee AC, Harris JP, Calvert JE. Impairments of mental rotation in Parkinson’s disease. Neuropsychologia 1998; 36(1):109–114.

    Article  CAS  PubMed  Google Scholar 

  46. Cronin Golomb A, Braun AE. Visuospatial dysfunction and problem solving in Parkinson’s disease. Neuropsychology 1997; 11(1):44–52.

    Article  CAS  PubMed  Google Scholar 

  47. Glosser G. Neurobehavioral aspects of movement disorders. Mov Disord 2001; 19(3):535–551.

    CAS  Google Scholar 

  48. Beatty WW. Cognition in a patient with very mild right-sided hemiparkinsonism. Neurocase 2002; 8(1–2):28–39.

    Article  PubMed  Google Scholar 

  49. Mathis C, Aoyama S, Kobayashi M, Borrelli E. Neurobiological features of dopamine D2 receptor knockout mice. Bolis CL, Pani L, Licinio J, eds. Dopaminergic System: Evolution from Biology to Clinical Aspects. Philadelphia: Lippincott Williams & Wilkins Healthcare, 2001:17–24.

    Google Scholar 

  50. Jones SR, Gainetdinov RR, Hu XT, Cooper DC, Wightman RM, White FJ, et al. Loss of autoreceptor functions in mice lacking the dopamine transporter. Nat Neurosci 1999; 2(7):649–655.

    Article  CAS  PubMed  Google Scholar 

  51. Gainetdinov RR, Mohn AR, Bohn LM, Caron MG. Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter. Proc Natl Acad Sci USA 2001; 98(20):11047–11054.

    Article  CAS  PubMed  Google Scholar 

  52. Miller GW, Gainetdinov RR, Levey AI, Caron MG. Dopamine transporters and neuronal injury. Trends Pharmacol Sci 1999; 20:424–429.

    Article  CAS  PubMed  Google Scholar 

  53. Charbonneau D, Riopelle RJ, Beninger RJ. Impaired incentive learning in treated Parkinson’s disease. Can J Neuro Sci 1996; 23(4):271–278.

    CAS  Google Scholar 

  54. Albin RL, Makowiec RL, Hollingsworth ZR, Dure LS, Penney JB, Young AB. Excitatory amino acid binding sites in the basal ganglia of the rat: a quantitative autoradiographic study. Neuroscience 1992; 46(1):35–48.

    Article  CAS  PubMed  Google Scholar 

  55. Schmidt WJ, Bury D. Behavioural effects of N-methyl-d-aspartate in the anterodorsal striatum of the rat. Life Sci 1988; 43:545–549.

    Article  CAS  PubMed  Google Scholar 

  56. Schmidt WJ, Kretschmer BD. Behavioural pharmacology of glutamate receptors in the basal ganglia. Neurosci Biobehav Rev 1997; 21(4):381–392.

    Article  CAS  PubMed  Google Scholar 

  57. Amalric M, Ougazzal A, Baunez C, Nieoullon A. Functional interactions between glutamate and dopamine in the rat striatum. Neurochem Int 1994; 25(2):123–131.

    Article  CAS  PubMed  Google Scholar 

  58. Baunez C, Amalric M. Evidence for functional differences between entopeduncular nucleus and substantia nigra: Effects of APV (DL-2-amino-5-phosphonovaleric acid) microinfusion on reaction time performance in the rat. Eur J Neurosci 1996; 8:1972–1982.

    Article  CAS  PubMed  Google Scholar 

  59. Schmidt WJ, Bubser M. Anticataleptic effects of the N-methyl-d-aspartate antagonist MK-801 in rats. Pharmacol Biochem Behav 1989; 32:621–623.

    Article  CAS  PubMed  Google Scholar 

  60. Schmidt WJ, Reichmann H. Parkinson’s Disease. In: Lodge D, Danysz W, Parsons CG, eds., Ionotropic Glutamate Receptors as Therapeutic Targets. Johnson City, TN: FP Graham Publishing, 2002:185–204.

    Google Scholar 

  61. Tzschentke TM. Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 1998; 56:613–672.

    Article  CAS  PubMed  Google Scholar 

  62. Graybiel AM, Canales JJ, Capper-Loup C. Levodopa-induced dyskinesias and dopaminedependent stereotypies: a new hypothesis. Trends Neurosci 2000; 23(19)Suppl:S71–S77.

    Article  CAS  PubMed  Google Scholar 

  63. Schmidt WJ, Tzschentke TM, Kretschmer BD. State-dependent blockade of haloperidolinduced sensitization of catalepsy by MK-801. Eur J Neurosci 1999; 11:3365–3368.

    Article  CAS  PubMed  Google Scholar 

  64. Lanis A, Schmidt WJ. NMDA receptor antagonists do not block the development of sensitization of catalepsy, but make its expression state-dependent. Behav Pharmacol 2001; 12:143–149.

    CAS  PubMed  Google Scholar 

  65. Chase TN, Engber M, Maral Mouradian M. Contribution of dopaminergic and glutamatergic mechanisms to the pathogenesis of motor response complications in Parkinson’s disease. Adv Neurol 1996; 69:497–501.

    CAS  PubMed  Google Scholar 

  66. Karcz-Kubicha M, Quack G, Danysz W. Amantadine attenuates response alterations resulting from repetitive L-dopa treatment in rats. J Neural Transm 1998; 105:1229–1236.

    Article  CAS  PubMed  Google Scholar 

  67. Konitsiotis S, Blanchet PJ, Verhagen L, Lamers E, Chase TN. AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology 2000;54:1589–1595.

    CAS  PubMed  Google Scholar 

  68. Verhagen Metman L, Oh JD. Dyskinesias in Parkinson’s disease. In: Lodge D, Danysz W, Parsons CG, eds., Ionotropic Glutamate Receptors as Therapeutic Targets. Johnson City, TN: FP Graham Publishing, 2002:205–227.

    Google Scholar 

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Authors and Affiliations

  1. Department of Neuropharmacology, Zoological Institute, University of Tuebingen, Tuebingen, Germany

    Werner J. Schmidt PhD

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  1. Werner J. Schmidt PhD
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Editors and Affiliations

  1. Department of Neuropharmacology Zoological Institute, University of Tübingen, Tübingen, Germany

    Werner J. Schmidt PhD

  2. Department of Psychiatry, New York University School of Medicine, New York, NY

    Maarten E. A. Reith PhD

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© 2005 Humana Press Inc., Totowa, NJ

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Schmidt, W.J. (2005). Dopamine and Glutamate in Motor and Cognitive Symptoms of Parkinson’s Disease. In: Schmidt, W.J., Reith, M.E.A. (eds) Dopamine and Glutamate in Psychiatric Disorders. Humana Press. https://doi.org/10.1007/978-1-59259-852-6_22

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  • DOI: https://doi.org/10.1007/978-1-59259-852-6_22

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-325-1

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