Skip to main content
SpringerLink
Log in

Symptomatic Models of Parkinson’s Disease and L-DOPA-Induced Dyskinesia in Non-human Primates

  • Chapter
  • First Online:
Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 22))

Abstract

Models of Parkinson’s disease (PD) can be produced in several non-human primate (NHP) species by applying neurotoxic lesions to the nigrostriatal dopamine pathway. The most commonly used neurotoxin is MPTP, a compound accidentally discovered as a contaminant of street drugs. Compared to other neurotoxins, MPTP has the advantage of crossing the blood–brain barrier and can thus be administered systemically. MPTP-lesioned NHPs exhibit the main core clinical features of PD. When treated with L-DOPA, these NHP models develop involuntary movements resembling the phenomenology of human dyskinesias. In old-world NHP species (macaques, baboons), choreic and dystonic dyskinesias can be readily distinguished and quantified with specific rating scales. More recently, certain non-motor symptoms relevant to human PD have been described in L-DOPA-treated MPTP-NHPs, including a range of neuropsychiatric abnormalities and sleep disturbances. The main shortcomings of MPTP-NHP models consist in a lack of progression of the underlying neurodegenerative lesion, along with an inability to model the intracellular protein-inclusion pathology typical of PD. The strength of MPTP-NHP models lies in their face and predictive validity for symptomatic treatments of parkinsonian motor features. Indeed, these models have been instrumental to the development of several medical and surgical approaches that are currently applied to treat PD.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
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

  • Akai T, Ozawa M, Yamaguchi M, Mizuta E, Kuno S (1995) Combination treatment of the partial D2 agonist terguride with the D1 agonist SKF 82958 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys. J Pharmacol Exp Ther 273:14–309

    Google Scholar 

  • Alexander GM, Schwartzman RJ, Brainard L, Gordon SW, Grothusen JR (1992) Changes in brain catecholamines and dopamine uptake sites at different stages of MPTP parkinsonism in monkeys. Brain Res 588:9–261

    Article  Google Scholar 

  • Annett LE, Torres EM, Ridley RM, Baker HF, Dunnett SB (1995) A comparison of the behavioural effects of embryonic nigral grafts in the caudate nucleus and in the putamen of marmosets with unilateral 6-OHDA lesions. Exp Brain Res 103:71–355

    Article  Google Scholar 

  • Apicella P, Trouche E, Nieoullon A, Legallet E, Dusticier N (1990) Motor impairments and neurochemical changes after unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system in monkeys. Neuroscience 38:66–655

    Article  Google Scholar 

  • Aziz TZ, Peggs D, Sambrook MA, Crossman AR (1991) Lesion of the subthalamic nucleus for the alleviation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the primate. Mov Disord 6:92–288

    Article  Google Scholar 

  • Bankiewicz KS, Oldfield EH, Chiueh CC, Doppman JL, Jacobowitz DM, Kopin IJ (1986) Hemiparkinsonism in monkeys after unilateral internal carotid artery infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Life Sci 39:7–16

    Article  CAS  PubMed  Google Scholar 

  • Barraud Q, Lambrecq V, Forni C, McGuire S, Hill M, Bioulac B, Balzamo E, Bezard E, Tison F, Ghorayeb I (2009) Sleep disorders in Parkinson’s disease: the contribution of the MPTP non-human primate model. Exp Neurol 219:82–574

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Bergman H, Raz A, Feingold A, Nini A, Nelken I, Hansel D, Ben-Pazi H, Reches A (1998) Physiology of MPTP tremor. Mov Disord 13(Suppl 3):29–34

    PubMed  Google Scholar 

  • Bezard E, Imbert C, Deloire X, Bioulac B, Gross CE (1997) A chronic MPTP model reproducing the slow evolution of Parkinson’s disease: evolution of motor symptoms in the monkey. Brain Res 766:12–107

    Article  Google Scholar 

  • Blanchet PJ, Calon F, Martel JC, Bédard PJ, Di Paolo T, Walters RR, Piercey MF (1995) Continuous administration decreases and pulsatile administration increases behavioral sensitivity to a novel dopamine D2 agonist (U-91356A) in MPTP-exposed monkeys. J Pharmacol Exp Ther 272(2):9–854

    Google Scholar 

  • Blanchet PJ, Konitsiotis S, Chase TN (1998) Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. Mov Disord 13:798–802

    Article  CAS  PubMed  Google Scholar 

  • Boyce S, Clarke CE, Luquin R, Peggs D, Robertson RG, Mitchell IJ, Sambrook MA, Crossman AR (1990a) Induction of chorea and dystonia in parkinsonian primates. Mov Disord 5:3–7

    Article  CAS  PubMed  Google Scholar 

  • Boyce S, Rupniak NM, Steventon MJ, Iversen SD (1990b) Characterisation of dyskinesias induced by L-dopa in MPTP-treated squirrel monkeys. Psychopharmacology 102:7–21

    Article  Google Scholar 

  • Brotchie JM (2005) Nondopaminergic mechanisms in levodopa-induced dyskinesia. Mov Disord 20:31–919

    Article  Google Scholar 

  • Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A 80:50–4546

    Google Scholar 

  • Campos-Romo A, Ojeda-Flores R, Moreno-Briseno P, Fernandez-Ruiz J (2009) Quantitative evaluation of MPTP-treated nonhuman parkinsonian primates in the HALLWAY task. J Neurosci Methods 177:8–361

    Article  Google Scholar 

  • Chu Y, Kordower JH (2007) Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson’s disease? Neurobiol Dis 25:49–134

    Article  Google Scholar 

  • Clarke CE, Sambrook MA, Mitchell IJ, Crossman AR (1987) Levodopa-induced dyskinesia and response fluctuations in primates rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). J Neurol Sci 78:80–273

    Google Scholar 

  • Crossman AR, Mitchell IJ, Sambrook MA (1985) Regional brain uptake of 2-deoxyglucose in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the macaque monkey. Neuropharmacology 24:91–587

    Article  Google Scholar 

  • Decamp E, Schneider JS (2009) Interaction between nicotinic and dopaminergic therapies on cognition in a chronic Parkinson model. Brain Res 1262:109–114. http://www.ncbi.nlm.nih.gov/pubmed/19368843

  • DeLong MR, Crutcher MD, Georgopoulos AP (1985) Primate globus pallidus and subthalamic nucleus: functional organization. J Neurophysiol 53:43–530

    Google Scholar 

  • Di Monte DA, McCormack A, Petzinger G, Janson AM, Quik M, Langston WJ (2000) Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model. Mov Disord 15(3):66–459

    Google Scholar 

  • Emborg ME (2007) Nonhuman primate models of Parkinson’s disease. ILAR J 48:55–339

    Article  Google Scholar 

  • Eslamboli A (2005) Marmoset monkey models of Parkinson’s disease: which model, when and why? Brain Res Bull 68:9–140

    Article  Google Scholar 

  • Everett GM, Blockus LE, Shepperd IM (1956) Tremor induced by tremorine and its antagonism by anti-Parkinson drugs. Science 79:124

    Google Scholar 

  • Forno LS, Langston JW, DeLanney LE, Irwin I, Ricaurte GA (1986) Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 20:55–449

    Google Scholar 

  • Fox SH, Brotchie JM (2010) The MPTP lesioned non-human primate models of PD; Past, present and future. Prog Brain Research 184:133–157

    CAS  Google Scholar 

  • Fox SH, Henry B, Hill MP, Peggs D, Crossman AR, Brotchie JM (2001) Neural mechanisms underlying peak-dose dyskinesia induced by levodopa and apomorphine are distinct: evidence from the effects of the alpha(2) adrenoceptor antagonist idazoxan. Mov Disord 16:50–642

    Article  Google Scholar 

  • Fox SH, Lang AE, Brotchie JM (2006a) 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 21:94–1578

    Article  Google Scholar 

  • Fox SH, Visanji NP, Johnston TH, Gomez-Ramirez J, Voon V, Brotchie JM (2006b) Dopamine receptor agonists and levodopa and inducing psychosis-like behavior in the MPTP primate model of Parkinson disease. Arch Neurol 63:4–1343

    Google Scholar 

  • Fox SH, Visanji NP, Reyes G, Huot P, Gomez-Ramirez J, Johnston TH, Brotchie JM (2010) Development of psychosis-like behaviors and motor complications with de novo levodopa treatment in the MPTP primate model of Parkinson’s disease. Can J Neurol Sci 37:86–95

    Article  PubMed  Google Scholar 

  • Fox SH, Johnston TH, Li Q, Brotchie J, Bezard E (2012) A critique of available scales and presentation of the Non-Human Primate Dyskinesia Rating Scale. Mov Disord 27(11):8–1373

    Article  Google Scholar 

  • Gibb WR, Lees AJ, Wells FR, Barnard RO, Jenner P, Marsden CD (1987) Pathology of MPTP in the marmoset. Adv Neurol 45:90–187

    Google Scholar 

  • Gomez-Mancilla B, Bedard PJ (1993) Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys. Clin Neuropharmacol 16:27–418

    Article  Google Scholar 

  • Gomez-Ramirez J, Johnston TH, Visanji NP, Fox SH, Brotchie JM (2006) Histamine H3 receptor agonists reduce L-dopa-induced chorea, but not dystonia, in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 21:46–839

    Article  Google Scholar 

  • Grabli D, Karachi C, Folgoas E, Monfort M, Tande D, Clark S, Civelli O, Hirsch EC, Francois C (2013) Gait disorders in parkinsonian monkeys with pedunculopontine nucleus lesions: a tale of two systems. J Neurosci 33:93–11986

    Google Scholar 

  • Halliday G, Herrero MT, Murphy K, McCann H, Ros-Bernal F, Barcia C, Mori H, Blesa FJ, Obeso JA (2009) No Lewy pathology in monkeys with over 10 years of severe MPTP Parkinsonism. Mov Disord 24:23–1519

    Article  Google Scholar 

  • Hatami A, Chesselet MF (2014) Transgenic rodent models to study alpha-synuclein pathogenesis with a focus on cognitive deficits, Current Topics in Behavioural Neuroscience, In press

    Google Scholar 

  • Henry B, Fox SH, Peggs D, Crossman AR, Brotchie JM (1999) The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTP-lesioned primate model of Parkinson’s disease. Mov Disord 14:53–744

    Google Scholar 

  • Hyacinthe C, Imbert C, Barraud Q, Tison F, Bezard E, Ghorayeb I (2014) D1 receptor agonist improves sleep-wake parameters in experimental parkinsonism. Neurobiol Dis 63:4–20

    Article  Google Scholar 

  • Iravani MM, Syed E, Jackson MJ, Johnston LC, Smith LA, Jenner P (2005) A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets. Eur J Neurosci 21:54–841

    Article  Google Scholar 

  • Jenner P (2003a) The contribution of the MPTP-treated primate model to the development of new treatment strategies for Parkinson’s disease. Parkinsonism Relat Disord 9:7–131

    Article  Google Scholar 

  • Jenner P (2003b) The MPTP-treated primate as a model of motor complications in PD: primate model of motor complications. Neurology 61:S4–11

    Article  CAS  PubMed  Google Scholar 

  • Jenner P, Rupniak NM, Rose S, Kelly E, Kilpatrick G, Lees A, Marsden CD (1984) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset. Neurosci Lett 50:85–90

    Article  CAS  PubMed  Google Scholar 

  • Johnston TH, Savola JM, Fox SH, Brotchie JM (2010) The α2 adrenergic antagonist fipamezole prolongs the anti-parkinsonian actions of L-DOPA in the MPTP-lesioned macaque. Mov Disord 25(13):93–2084

    Google Scholar 

  • Kalia L, Brotchie JM, Fox SH (2013) Novel nondopaminergic targets for motor features of Parkinson’s disease: Review of recent trials. Mov Disord 28:44–131

    Article  Google Scholar 

  • Karachi C, Grabli D, Bernard FA, Tande´ D, Wattiez N, Belaid H, Bardinet E,Prigent A, Nothacker HP, Hunot S, Hartmann A, Lehericy S, Hirsch EC, Francois C (2010) Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease. J Clin Invest 120:2745–2754

    Google Scholar 

  • Kowall NW, Hantraye P, Brouillet E, Beal MF, McKee AC, Ferrante RJ (2000) MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons. NeuroReport 11:3–211

    Article  Google Scholar 

  • Kuoppamaki M, Al-Barghouthy G, Jackson M, Smith L, Zeng BY, Quinn N, Jenner P (2002) Beginning-of-dose and rebound worsening in MPTP-treated common marmosets treated with levodopa. Mov Disord 17:7–1312

    Article  Google Scholar 

  • Langston JW, Langston EB, Irwin I (1984) MPTP-induced parkinsonism in human and non-human primates–clinical and experimental aspects. Acta Neurol Scand Suppl 100:49–54

    CAS  PubMed  Google Scholar 

  • Lieu CA, Deogaonkar M, Bakay RA (2011) Subramanian T Dyskinesias do not develop after chronic intermittent levodopa therapy in clinically hemiparkinsonian rhesus monkeys. Parkinsonism Relat Disord. 17(1):9–34

    Article  Google Scholar 

  • Liu N, Yue F, Tang WP, Chan P (2009) An objective measurement of locomotion behavior for hemiparkinsonian cynomolgus monkeys. J Neurosci Methods 183:94–188

    Google Scholar 

  • Meissner W, Prunier C, Guilloteau D, Chalon S, Gross CE, Bezard E (2003) Time-course of nigrostriatal degeneration in a progressive MPTP-lesioned macaque model of Parkinson’s disease. Mol Neurobiol 28:18–209

    Article  Google Scholar 

  • Mestre TJT, Brotchie JM, Fox S (2010) Evolution of the “short duration” response to L-DOPA in the MPTP-lesioned non-human primate model of Parkinson’s disease. Mov Disord 25(Suppl 2):S417

    Google Scholar 

  • Mitchell IJ, Cross AJ, Sambrook MA, Crossman AR (1985) Sites of the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the macaque monkey include the ventral tegmental area and the locus coeruleus. Neurosci Lett 61:195–200

    Article  CAS  PubMed  Google Scholar 

  • Nandi D, Jenkinson N, Stein J, Aziz T (2008) The pedunculopontine nucleus in Parkinson’s disease: primate studies. Br J Neurosurg 22, Suppl 1:S4–8

    Google Scholar 

  • Nutt JG, Carter JH, Lea ES, Sexton GJ (2002) Evolution of the response to levodopa during the first 4 years of therapy. Ann Neurol 51:93–686

    Article  Google Scholar 

  • Obeso JA, Rodriguez-Oroz MC, Rodriguez M, DeLong MR, Olanow CW (2000) Pathophysiology of levodopa-induced dyskinesias in Parkinson’s disease: problems with the current model. Ann Neurol 47:S22-32, discussion S32-4

    Google Scholar 

  • Ovadia A, Zhang Z, Gash DM (1995) Increased susceptibility to MPTP toxicity in middle-aged rhesus monkeys. Neurobiol Aging 16:7–931

    Article  Google Scholar 

  • Pearce RK, Jackson M, Smith L, Jenner P, Marsden CD (1995) Chronic L-DOPA administration induces dyskinesias in the 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-treated common marmoset (Callithrix Jacchus). Mov Disord 10:40–731

    Google Scholar 

  • Perez-Otano I, Herrero MT, Oset C, De Ceballos ML, Luquin MR, Obeso JA, Del Rio J (1991) Extensive loss of brain dopamine and serotonin induced by chronic administration of MPTP in the marmoset. Brain Res 567:32–127

    Google Scholar 

  • Perez-Otano I, Oset C, Luquin MR, Herrero MT, Obeso JA, Del Rio J (1994) MPTP-induced parkinsonism in primates: pattern of striatal dopamine loss following acute and chronic administration. Neurosci Lett 175:5–121

    Article  Google Scholar 

  • Pessiglione M, Guehl D, Jan C, Francois C, Hirsch EC, Feger J, Tremblay L (2004) Disruption of self-organized actions in monkeys with progressive MPTP-induced parkinsonism: II. Effects of reward preference. Eur J Neurosci 19:46–437

    Google Scholar 

  • Petzinger GM, Quik M, Ivashina E, Jakowec MW, Jakubiak M, Di Monte D, Langston JW (2001) Reliability and validity of a new global dyskinesia rating scale in the MPTP-lesioned non-human primate. Mov Disord 16(2):7–202

    Article  Google Scholar 

  • Pifl C, Schingnitz G, Hornykiewicz O (1991) Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on the regional distribution of brain monoamines in the rhesus monkey. Neuroscience 44:591–605

    Article  CAS  PubMed  Google Scholar 

  • Pifl C, Hornykiewicz O, Blesa J, Adánez R, Cavada C, Obeso JA (2013) Reduced noradrenaline, but not dopamine and serotonin in motor thalamus of the MPTP primate: relation to severity of parkinsonism. J Neurochem 125:62–657

    Article  Google Scholar 

  • Poirier LJ (1960) Experimental and histological study of midbrain dyskinesias. J Neurophysiol 23:51–534

    Google Scholar 

  • Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J (2009) Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 72:300–1296

    Article  Google Scholar 

  • Przedborski S, Jackson-Lewis V, Naini AB, Jakowec M, Petzinger G, Miller R, Akram M (2001) The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem 76:74–1265

    Google Scholar 

  • Quinn NP (1998) Classification of fluctuations in patients with Parkinson’s disease. Neurology 51:S25–9

    Google Scholar 

  • Revuelta GJ, Uthayathas S, Wahlquist AE, Factor SA, Papa SM (2012) Non-human primate FOG develops with advanced parkinsonism induced by MPTP Treatment. Exp Neurol 237(2):9–464

    Article  Google Scholar 

  • Rose S, Nomoto M, Jenner P, Marsden CD (1989) Transient depletion of nucleus accumbens dopamine content may contribute to initial akinesia induced by MPTP in common marmosets. Biochem Pharmacol 38:81–3677

    Article  Google Scholar 

  • Russ H, Mihatsch W, Gerlach M, Riederer P, Przuntek H (1991) Neurochemical and behavioural features induced by chronic low dose treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset: implications for Parkinson’s disease? Neurosci Lett 123:8–115

    Article  Google Scholar 

  • Schneider JS (1989) Levodopa-induced dyskinesias in parkinsonian monkeys: relationship to extent of nigrostriatal damage. Pharmacol Biochem Behav 34(1):6–193

    Article  Google Scholar 

  • Schneider JS, Kovelowski CJ 2nd (1990) Chronic exposure to low doses of MPTP. I. Cognitive deficits in motor asymptomatic monkeys. Brain Res 519:8–122

    Article  Google Scholar 

  • Schneider JS, Gonczi H, Decamp E (2003) Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and/or duration of symptoms. Brain Res 990:38–44

    Article  CAS  PubMed  Google Scholar 

  • Smith LA, Jackson MJ, Hansard MJ, Maratos E, Jenner P (2003) Effect of pulsatile administration of levodopa on dyskinesia induction in drug-naive MPTP-treated common marmosets: effect of dose, frequency of administration, and brain exposure. Mov Disord 18:95–487

    Article  Google Scholar 

  • Taylor JR, Elsworth JD, Roth RH, Sladek JR Jr, Redmond DE Jr (1990) Cognitive and motor deficits in the acquisition of an object retrieval/detour task in MPTP-treated monkeys. Brain 113(Pt 3):37–617

    Google Scholar 

  • Taylor JR, Elsworth JD, Roth RH, Sladek JR Jr, Redmond DE Jr (1997) Severe long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the vervet monkey (Cercopithecus aethiops sabaeus). Neuroscience 81:55–745

    Article  Google Scholar 

  • Todd RD, Carl J, Harmon S, O’Malley KL, Perlmutter JS (1996) Dynamic changes in striatal dopamine D2 and D3 receptor protein and mRNA in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) denervation in baboons. J Neurosci 16:82–7776

    Google Scholar 

  • Togasaki DM, Hsu A, Samant M, Farzan B, DeLanney LE, Langston JW, Di Monte DA, Quik M (2005) The Webcam system: a simple, automated, computer-based video system for quantitative measurement of movement in nonhuman primates. J Neurosci Methods 145:66–159

    Article  Google Scholar 

  • Verhave PS, Jongsma MJ, Van den Berg RM, Vis JC, Vanwersch RA, Smit AB, Van Someren EJ, Philippens IH (2011) REM sleep behavior disorder in the marmoset MPTP model of early Parkinson disease. Sleep 34(8):25–1119

    Google Scholar 

  • Vezoli J, Fifel K, Leviel V, Dehay C, Kennedy H, Cooper HM, Gronfier C, Procyk E (2011) Early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a MPTP-monkey model of Parkinson’s disease. PLoS ONE 6(8):e23952

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Villalba RM, Lee H, Smith Y (2009) Dopaminergic denervation and spine loss in the striatum of MPTP-treated monkeys. Exp Neurol 215:7–220

    Article  Google Scholar 

  • Visanji NP, Brotchie JM (2005) MPTP-induced models of Parkinson’s disease in mice and non-human primates. Curr Protoc Pharmacol Chapter 5:Unit5.42

    Google Scholar 

  • Visanji NP, Gomez-Ramirez J, Johnston TH, Pires D, Voon V, Brotchie JM, Fox SH (2006) Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 21:91–1879

    Article  Google Scholar 

  • Visanji NP, Fox SH, Johnston T, Reyes G, Millan MJ, Brotchie JM (2009a) Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson’s disease. Neurobiol Dis 35:92–184

    Article  Google Scholar 

  • Visanji NP, Fox SH, Johnston TH, Millan MJ, Brotchie JM (2009b) Alpha1-adrenoceptors mediate dihydroxyphenylalanine-induced activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaques. J Pharmacol Exp Ther 328:83–276

    Article  Google Scholar 

  • Voon V, Fox SH (2007) Medication-related impulse control and repetitive behaviors in Parkinson disease. Arch Neurol 64:96–1089

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Toronto Western Research Institute, University of Toronto, Toronto Western Hospital, 399, Bathurst St, Toronto, ON, M5T 2S8, Canada

    Tom M. Johnston

  2. Division of Neurology, University of Toronto, Toronto Western Hospital, 399, Bathurst St, Toronto, ON, M5T 2S8, Canada

    Susan H. Fox

Authors
  1. Tom M. Johnston
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan H. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan H. Fox .

Editor information

Editors and Affiliations

  1. Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany

    Hoa Huu Phuc Nguyen

  2. Dept of Experimental Medical Science, Lund University, Lund, Sweden

    M. Angela Cenci

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Johnston, T.M., Fox, S.H. (2014). Symptomatic Models of Parkinson’s Disease and L-DOPA-Induced Dyskinesia in Non-human Primates. In: Nguyen, H., Cenci, M. (eds) Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease. Current Topics in Behavioral Neurosciences, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2014_352

Download citation

Publish with us

Policies and ethics

Search

Navigation