Skip to main content
SpringerLink
Log in

Animal models of l-DOPA-induced dyskinesia: the 6-OHDA-lesioned rat and mouse

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Appearance of l-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor l-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9–10 years of l-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson’s disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i.e., LID) and to screen for new potential anti-parkinsonian and anti-dyskinetic treatments. Among all the models developed, the 6-OHDA-lesioned rodents represent the models of choice to mimic PD motor symptoms and LID, thanks to their reproducibility and translational value. Under l-DOPA treatment, rodents sustaining 6-OHDA lesions develop abnormal involuntary movements with dystonic and hyperkinetic features, resembling what seen in dyskinetic PD patients. These models have been extensively validated by the evidence that dyskinetic behaviors are alleviated by compounds reducing dyskinesia in patients and non-human primate models of PD. This article will focus on the translational value of the 6-OHDA rodent models of LID, highlighting their main features, advantages and disadvantages in preclinical research.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alcacer C, Andreoli L, Sebastianutto I et al (2017) Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson’s disease therapy. J Clin Investig 127:720–734

    Article  PubMed  Google Scholar 

  • Amalric M, Moukhles H, Nieoullon A, Daszuta A (1995) Complex deficits on reaction time performance following bilateral intrastriatal 6-OHDA infusion in the rat. Eur J Neurosci 7:972–980

    Article  PubMed  CAS  Google Scholar 

  • Andersson M, Hilbertson A, Cenci MA (1999) Striatal fosB expression is causally linked with l-DOPA-induced abnormal involuntary movements and the associated upregulation of striatal prodynorphin mRNA in a rat model of Parkinson’s disease. Neurobiol Dis 6:461–474

    Article  PubMed  CAS  Google Scholar 

  • Antonini A, Ursino G, Calandrella D et al (2010) Continuous dopaminergic delivery in Parkinson’s disease. J Neurol 257:S305–S308

    Article  PubMed  CAS  Google Scholar 

  • Bastide MF, Meissner WG, Picconi B et al (2015) Pathophysiology of l-dopa-induced motor and non-motor complications in Parkinson’s disease. Prog Neurobiol 132:96–168

    Article  PubMed  CAS  Google Scholar 

  • Berton O, Guigoni C, Li Q et al (2009) Striatal overexpression of DeltaJunD resets l-DOPA-induced dyskinesia in a primate model of Parkinson disease. Biol Psychiatry 66:554–561

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bez F, Francardo V, Cenci MA (2016) Dramatic differences in susceptibility to l-DOPA-induced dyskinesia between mice that are aged before or after a nigrostriatal dopamine lesion. Neurobiol Dis 94:213–225

    Article  PubMed  CAS  Google Scholar 

  • Bezard E, Tronci E, Pioli EY et al (2013) Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia. Mov Disord 28:1088–1096

    Article  PubMed  CAS  Google Scholar 

  • Blesa J, Phani S, Jackson-Lewis V, Przedborski S (2012) Classic and new animal models of Parkinson’s disease. J Biomed Biotechnol 2012:845618

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bracco F, Battaglia A, Chouza C et al (2004) The long-acting dopamine receptor agonist cabergoline in early Parkinson’s disease: final results of a 5-year, double-blind, levodopa-controlled study. CNS Drugs 18:733–746

    Article  PubMed  CAS  Google Scholar 

  • Cao X, Yasuda T, Uthayathas S et al (2010) Striatal overexpression of DeltaFosB reproduces chronic levodopa-induced involuntary movements. J Neurosci 30:7335–7343

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180:1200

    Article  PubMed  CAS  Google Scholar 

  • Carta M, Tronci E (2014) Serotonin system implication in l-DOPA-induced dyskinesia: from animal models to clinical investigations. Front Neurol 5:78

    Article  PubMed  PubMed Central  Google Scholar 

  • Carta M, Carlsson T, Kirik D et al (2007) Dopamine released from 5-HT terminals is the cause of l-DOPA-induced dyskinesia in parkinsonian rats. Brain 130:1819–1833

    Article  PubMed  Google Scholar 

  • Carta M, Carlsson T, Muñoz A et al (2008) Involvement of the serotonin system in l-dopa-induced dyskinesias. Parkinsonism Relat Disord 14(Suppl 2):S154–S158

    Article  PubMed  Google Scholar 

  • Carta M, Carlsson T, Muñoz A et al (2010) Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson’s disease. Mov Disord 25:S174–S179

    Article  PubMed  Google Scholar 

  • Cenci MA, Konradi C (2010) Maladaptive striatal plasticity in l-DOPA-induced dyskinesia. Prog Brain Res 183:209–233

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cenci MA, Lee CS, Björklund A (1998) l-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA. Eur J Neurosci 10:2694–2706

    Article  PubMed  CAS  Google Scholar 

  • Cenci MA, Ohlin KE, Rylander D (2009) Plastic effects of l-DOPA treatment in the basal ganglia and their relevance to the development of dyskinesia. Parkinsonism Relat Disord 15(Suppl 3):S59–S63

    Article  PubMed  Google Scholar 

  • Cicchetti F, Brownell AL, Williams K et al (2002) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15:991–998

    Article  PubMed  CAS  Google Scholar 

  • Cohen G (1984) Oxy-radical toxicity in catecholamine neurons. Neurotoxicology 5:77–82

    PubMed  CAS  Google Scholar 

  • Date I, Felten DL, Felten SY (1990) Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis. Brain Res 519:266–276

    Article  PubMed  CAS  Google Scholar 

  • de la Fuente-Fernández R, Sossi V, Huang Z et al (2004) Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias. Brain 127:2747–2754

    Article  PubMed  Google Scholar 

  • De Leonibus E, Pascucci T, Lopez S et al (2007) Spatial deficits in a mouse model of Parkinson disease. Psychopharmacology 194:517–525

    Article  PubMed  CAS  Google Scholar 

  • Decressac M, Mattsson B, Björklund A (2012) Comparison of the behavioural and histological characteristics of the 6-OHDA and α-synuclein rat models of Parkinson’s disease. Exp Neurol 235:306–315

    Article  PubMed  CAS  Google Scholar 

  • Dekundy A, Lundblad M, Danysz W, Cenci MA (2007) Modulation of l-DOPA-induced abnormal involuntary movements by clinically tested compounds: further validation of the rat dyskinesia model. Behav Brain Res 179:76–89

    Article  PubMed  CAS  Google Scholar 

  • Delfino M, Stefano A, Ferrario J et al (2004) Behavioral sensitization to different dopamine agonists in a parkinsonian rodent model of drug-induced dyskinesias. Behav Brain Res 152:297–306

    Article  PubMed  CAS  Google Scholar 

  • Ding Y, Restrepo J, Won L et al (2007) Chronic 3,4-dihydroxyphenylalanine treatment induces dyskinesia in aphakia mice, a novel genetic model of Parkinson’s disease. Neurobiol Dis 27:11–23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Duty S, Jenner P (2011) Animal models of Parkinson’s disease: a source of novel treatments and clues to the cause of the disease. Br J Pharmacol 164:1357–1391

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fahn S (2003) Description of Parkinson's disease as a clinical syndrome. Ann N Y Acad Sci 991:1–14

    Article  PubMed  CAS  Google Scholar 

  • Fahn S (2015) The medical treatment of Parkinson disease from James Parkinson to George Cotzias. Mov Disord 30:4–18

    Article  PubMed  CAS  Google Scholar 

  • Fasano S, Bezard E, D’Antoni A et al (2010) Inhibition of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) signaling in the striatum reverts motor symptoms associated with l-dopa-induced dyskinesia. Proc Natl Acad Sci USA 107:21824–21829

    Article  PubMed  Google Scholar 

  • Francardo V, Cenci MA (2014) Investigating the molecular mechanisms of l-DOPA-induced dyskinesia in the mouse. Parkinsonism Relat Disord 20(Suppl 1):S20–S22

    Article  PubMed  Google Scholar 

  • Francardo V, Recchia A, Popovic N et al (2011) Impact of the lesion procedure on the profiles of motor impairment and molecular responsiveness to l-DOPA in the 6-hydroxydopamine mouse model of Parkinson’s disease. Neurobiol Dis 42:327–340

    Article  PubMed  CAS  Google Scholar 

  • Ghiglieri V, Mineo D, Vannelli A et al (2016) Modulation of serotonergic transmission by eltoprazine in l-DOPA-induced dyskinesia: behavioral, molecular, and synaptic mechanisms. Neurobiol Dis 86:140–153

    Article  PubMed  CAS  Google Scholar 

  • Henry B, Crossman AR, Brotchie JM (1998) Characterization of enhanced behavioral responses to l-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. Exp Neurol 151:334–342

    Article  PubMed  CAS  Google Scholar 

  • Hernández LF, Castela I, Ruiz-DeDiego I et al (2017) Striatal activation by optogenetics induces dyskinesias in the 6-hydroxydopamine rat model of Parkinson disease. Mov Disord 32:530–537

    Article  CAS  Google Scholar 

  • Holloway RG, Shoulson I, Fahn S et al (2004) Pramipexole vs levodopa as initial treatment for Parkinson disease. Arch Neurol 61:1044–1053

    PubMed  Google Scholar 

  • Hope BT, Nye HE, Kelz MB et al (1994) Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments. Neuron 13:1235–1244

    Article  PubMed  CAS  Google Scholar 

  • Iderberg H, Francardo V, Pioli EY (2012) Animal models of l-DOPA-induced dyskinesia: an update on the current options. Neurosci 211:13–27

    Article  PubMed  CAS  Google Scholar 

  • Iderberg H, McCreary AC, Varney MA et al (2015) Activity of serotonin 5-HT(1A) receptor “biased agonists” in rat models of Parkinson’s disease and l-DOPA-induced dyskinesia. Neuropharmacology 93:52–67

    Article  PubMed  CAS  Google Scholar 

  • Jackson-Lewis V, Przedborski S (2007) Protocol for the MPTP mouse model of Parkinson’s disease. Nat Protoc 2:141–151

    Article  PubMed  CAS  Google Scholar 

  • Jankovic J, Stacy M (2007) Medical management of levodopa-associated motor complications in patients with Parkinson’s disease. CNS Drugs 21:677–692

    Article  PubMed  CAS  Google Scholar 

  • Kirik D, Rosenblad C, Björklund A (1998) Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp Neurol 152:259–277

    Article  PubMed  CAS  Google Scholar 

  • Lindgren HS, Rylander D, Ohlin KE et al (2007) The “motor complication syndrome” in rats with 6-OHDA lesions treated chronically with l-DOPA: relation to dose and route of administration. Behav Brain Res 177:150–159

    Article  PubMed  CAS  Google Scholar 

  • Lindgren HS, Andersson DR, Lagerkvist S et al (2010) l-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson’s disease: temporal and quantitative relationship to the expression of dyskinesia. J Neurochem 112:1465–1476

    Article  PubMed  CAS  Google Scholar 

  • Lundblad M, Andersson M, Winkler C et al (2002) Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson’s disease. Eur J Neurosci 15:120–132

    Article  PubMed  CAS  Google Scholar 

  • Lundblad M, Picconi B, Lindgren H, Cenci MA (2004) A model of l-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Neurobiol Dis 16:110–123

    Article  PubMed  CAS  Google Scholar 

  • Lundblad M, Usiello A, Carta M et al (2005) Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia. Exp Neurol 194:66–75

    Article  PubMed  CAS  Google Scholar 

  • Manson A, Stirpe P, Schrag A (2012) Levodopa-induced-dyskinesias clinical features, incidence, risk factors, management and impact on quality of life. J Parkinsons Dis 2:189–198

    PubMed  CAS  Google Scholar 

  • Mazzio EA, Reams RR, Soliman KFA (2004) The role of oxidative stress, impaired glycolysis and mitochondrial respiratory redox failure in the cytotoxic effects of 6-hydroxydopamine in vitro. Brain Res 1004:29–44

    Article  PubMed  CAS  Google Scholar 

  • Mela F, Marti M, Bido S et al (2012) In vivo evidence for a differential contribution of striatal and nigral D1 and D2 receptors to l-DOPA induced dyskinesia and the accompanying surge of nigral amino acid levels. Neurobiol Dis 45:573–582

    Article  PubMed  CAS  Google Scholar 

  • Mitsumoto Y, Watanabe A, Mori A, Koga N (1998) Spontaneous regeneration of nigrostriatal dopaminergic neurons in MPTP-treated C57BL/6 mice. Biochem Biophys Res Commun 248:660–663

    Article  PubMed  CAS  Google Scholar 

  • Mulas G, Espa E, Fenu S et al (2016) Differential induction of dyskinesia and neuroinflammation by pulsatile versus continuous l-DOPA delivery in the 6-OHDA model of Parkinson’s disease. Exp Neurol 286:83–92

    Article  PubMed  CAS  Google Scholar 

  • Nadjar A, Gerfen CR, Bezard E (2009) Priming for l-dopa-induced dyskinesia in Parkinson’s disease: a feature inherent to the treatment or the disease? Prog Neurobiol 87:1–9

    Article  PubMed  CAS  Google Scholar 

  • Nicholas AP (2007) Levodopa-induced hyperactivity in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Mov Disord 22:99–104

    Article  PubMed  Google Scholar 

  • Olanow CW, Agid Y, Mizuno Y et al (2004) Levodopa in the treatment of Parkinson’s disease: current controversies. Mov Disord 19:997–1005

    Article  PubMed  Google Scholar 

  • Olsson M, Nikkhah G, Bentlage C, Björklund A (1995) Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J Neurosci 15:3863–3875

    Article  PubMed  CAS  Google Scholar 

  • Paillé V, Henry V, Lescaudron L et al (2007) Rat model of Parkinson’s disease with bilateral motor abnormalities, reversible with levodopa, and dyskinesias. Mov Disord 22:533–539

    Article  PubMed  Google Scholar 

  • Papa SM, Engber TM, Kask AM, Chase TN (1994) Motor fluctuations in levodopa treated parkinsonian rats: relation to lesion extent and treatment duration. Brain Res 662:69–74

    Article  PubMed  CAS  Google Scholar 

  • Papathanou M, Rose S, McCreary A, Jenner P (2011) Induction and expression of abnormal involuntary movements is related to the duration of dopaminergic stimulation in 6-OHDA-lesioned rats. Eur J Neurosci 33:2247–2254

    Article  PubMed  Google Scholar 

  • Paquette MA, Martinez AA, Macheda T et al (2012) Anti-dyskinetic mechanisms of amantadine and dextromethorphan in the 6-OHDA rat model of Parkinson’s disease: role of NMDA vs. 5-HT1A receptors. Eur J Neurosci 36:3224–3234

    Article  PubMed  PubMed Central  Google Scholar 

  • Pavón N, Martín AB, Mendialdua A, Moratalla R (2006) ERK phosphorylation and FosB expression are associated with l-DOPA-induced dyskinesia in hemiparkinsonian mice. Biol Psychiatry 59:64–74

    Article  PubMed  CAS  Google Scholar 

  • Perfeito R, Cunha-Oliveira T, Rego AC (2013) Reprint of: revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse. Free Radic Biol Med 62:186–201

    Article  PubMed  CAS  Google Scholar 

  • Picconi B, Paillé V, Ghiglieri V et al (2008) l-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation. Neurobiol Dis 29:327–335

    Article  PubMed  CAS  Google Scholar 

  • Pinna A, Morelli M (2014) A critical evaluation of behavioral rodent models of motor impairment used for screening of antiparkinsonian activity: the case of adenosine A2A receptor antagonists. Neurotox Res 25:392–401

    Article  PubMed  CAS  Google Scholar 

  • Pinna A, Ko WK, Costa G et al (2015) Antidyskinetic effect of A2A and 5HT1A/1B receptor ligands in two animal models of Parkinson’s disease. Mov Disord 31:501–511

    Article  CAS  Google Scholar 

  • Politis M, Wu K, Loane C et al (2014) Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients. J Clin Investig 124:1340–1349

    Article  PubMed  CAS  Google Scholar 

  • Przedborski S, Levivier M, Jiang H et al (1995) Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine. Neuroscience 67:631–647

    Article  PubMed  CAS  Google Scholar 

  • Putterman DB, Munhall AC, Kozell LB et al (2007) Evaluation of levodopa dose and magnitude of dopamine depletion as risk factors for levodopa-induced dyskinesia in a rat model of Parkinson’s disease. J Pharmacol Exp Ther 323:277–284

    Article  PubMed  CAS  Google Scholar 

  • Rascol O, Brooks DJ, Korczyn AD et al (2000) A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med 342:1484–1491

    Article  PubMed  CAS  Google Scholar 

  • Sahin G, Thompson LH, Lavisse S et al (2014) Differential dopamine receptor occupancy underlies l-DOPA-induced dyskinesia in a rat model of parkinson’s disease. PLoS One 9:e90759

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sakai K, Gash DM (1994) Effect of bilateral 6-OHDA lesions of the substantia nigra on locomotor activity in the rat. Brain Res 633:144–150

    Article  PubMed  CAS  Google Scholar 

  • Santini E, Valjent E, Usiello A et al (2007) Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in l-DOPA-induced dyskinesia. J Neurosci 27:6995–7005

    Article  PubMed  CAS  Google Scholar 

  • Sawada H, Oeda T, Kuno S et al (2010) Amantadine for dyskinesias in Parkinson’s disease: a randomized controlled trial. PLoS One 5:e15298

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schwarting RK, Huston JP (1996) The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Prog Neurobiol 50:275–331

    Article  PubMed  CAS  Google Scholar 

  • Sebastianutto I, Maslava N, Hopkins CR, Cenci MA (2016) Validation of an improved scale for rating l-DOPA-induced dyskinesia in the mouse and effects of specific dopamine receptor antagonists. Neurobiol Dis 96:156–170

    Article  PubMed  CAS  Google Scholar 

  • Sedelis M, Hofele K, Auburger GW et al (2000) MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences. Behav Genet 30:171–182

    Article  PubMed  CAS  Google Scholar 

  • Stocchi F, Vacca L, Ruggieri S, Olanow CW (2005) Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol 62:905–910

    Article  PubMed  Google Scholar 

  • Tanaka H, Kannari K, Maeda T et al (1999) Role of serotonergic neurons in l-DOPA-derived extracellular dopamine in the striatum of 6-OHDA-lesioned rats. NeuroReport 10:631–634

    Article  PubMed  CAS  Google Scholar 

  • Taylor JL, Bishop C, Walker PD (2005) Dopamine D1 and D2 receptor contributions to l-DOPA-induced dyskinesia in the dopamine-depleted rat. Pharmacol Biochem Behav 81:887–893

    Article  PubMed  CAS  Google Scholar 

  • Tronci E, Shin E, Björklund A, Carta M (2012) Amphetamine-induced rotation and l-DOPA-induced dyskinesia in the rat 6-OHDA model: a correlation study. Neurosci Res 73:168–172

    Article  PubMed  CAS  Google Scholar 

  • Tronci E, Lisci C, Stancampiano R et al (2013) 5-Hydroxy-tryptophan for the treatment of l-DOPA-induced dyskinesia in the rat Parkinson’s disease model. Neurobiol Dis 60:108–114

    Article  PubMed  CAS  Google Scholar 

  • Tronci E, Fidalgo C, Carta M (2014) The serotonergic system in l-DOPA-induced dyskinesia. In: Fox S, Brotchie J (eds) Levodopa-Induced Dyskinesia in Parkinson's Disease. Springer, London, pp 199–212

    Google Scholar 

  • Tronci E, Fidalgo C, Stancampiano R, Carta M (2015) Effect of selective and non-selective serotonin receptor activation on l-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats. Behav Brain Res 292:300–304

    Article  PubMed  CAS  Google Scholar 

  • Ulusoy A, Sahin G, Kirik D (2010) Presynaptic dopaminergic compartment determines the susceptibility to l-DOPA-induced dyskinesia in rats. Proc Natl Acad Sci 107:13159–13164

    Article  PubMed  Google Scholar 

  • Ungerstedt U (1968) 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5:107–110

    Article  PubMed  CAS  Google Scholar 

  • Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:69–93

    Article  PubMed  CAS  Google Scholar 

  • Westin JE, Vercammen L, Strome EM et al (2007) Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of l-DOPA-induced dyskinesia and the role of dopamine D1 receptors. Biol Psychiatry 62:800–810

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Winkler C, Kirik D, Björklund A, Dunnett SB (2000) Transplantation in the rat model of Parkinson’s disease: ectopic versus homotopic graft placement. Prog Brain Res 127:233–265

    Article  PubMed  CAS  Google Scholar 

  • Winkler C, Kirik D, Björklund A, Cenci MA (2002) L-DOPA-induced dyskinesia in the intrastriatal 6-hydroxydopamine model of Parkinson’s disease: relation to motor and cellular parameters of nigrostriatal function. Neurobiol Dis 10:165–186

    Article  PubMed  Google Scholar 

  • Zhang Z, Andersen A, Smith C et al (2010) Motor slowing and parkinsonian signs in aging rhesus monkeys mirror human aging. J Gerontol A Biol Sci Med Sci 55:B473–B480

    Article  Google Scholar 

Download references

Acknowledgements

Veronica Francardo is supported by grants from the Swedish Parkinson Foundation, The Greta and Johan Kocks Foundation, and the Michael J Fox Foundation.

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Cittadella Universitaria, SS554 Km 4.5, 09042, Monserrato, Italy

    Elisabetta Tronci

  2. Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden

    Veronica Francardo

Authors
  1. Elisabetta Tronci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Veronica Francardo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elisabetta Tronci.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tronci, E., Francardo, V. Animal models of l-DOPA-induced dyskinesia: the 6-OHDA-lesioned rat and mouse. J Neural Transm 125, 1137–1144 (2018). https://doi.org/10.1007/s00702-017-1825-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-017-1825-5

Keywords

Search

Navigation