Abstract
A significant proportion of patients with Parkinson’s disease (PD) receiving dopamine replacement therapy in the form of levodopa develop dyskinesia that becomes a major complicating factor in treatment. Dyskinesia can only be effectively treated by a reduction in drug dose, which limits efficacy, by co-administration of the weak NMDA antagonist amantadine or by surgical treatment (pallidotomy, DBS). This raises the important question of why dyskinesia occurs in PD and how it can be avoided or suppressed by pharmacological treatment. This review assesses some of the mechanisms that underlie dyskinesia induction and expression from presynaptic changes in dopaminergic neurones to postsynaptic alterations in basal ganglia function and examines potential approaches to prevention and treatment. These include glutamatergic approaches where agents that directly or indirectly alter glutamatergic neurotransmission modify the intracellular influx of Ca2+ and reduce the formation of nitric oxide by neuronal nitric oxide synthase that may form an integral component of the complex cascade of events leading to dyskinesia. There is increasing evidence for the role of serotoninergic neurones in dyskinesia induction related to non-physiological formation and release of dopamine and serotoninergic agonists can modify dyskinesia expression. Similarly, noradrenergic receptors may serve to alter dyskinesia intensity and α-2-adrenoceptor antagonists alter the expression of levodopa-induced dyskinesia in both experimental models of PD and in man. Finally, other potential approaches to dyskinesia treatment based on manipulation of opiate, cannabinoid, adenosine and histamine receptors are considered. The conclusion is that the cause of levodopa-induced dyskinesia remains to be fully elucidated and that new approaches to treatment through non-dopaminergic mechanisms are required to control the onset and expression of involuntary movements.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahlskog JE (1999) Medical treatment of later-stage motor problems of Parkinson disease. Mayo Clin Proc 74(12):1239–1254
Ahlskog JE, Muenster MD (2001) Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 16(3):448–458
Alexander GM, Schwartzman RJ, Grothusen JR, Brainard L, Gordon SW (1993) Changes in brain dopamine receptors in MPTP parkinsonian monkeys following L-dopa treatment. Brain Res 625:276–282
Andersson M, Usiello A, Borgkvist A, Pozzi L, Dominguez C, Fienberg AA, Svenningsson P, Fredholm BB, Borrelli E, Greengard P, Fisone G (2005) Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons. J Neurosci 25(37):8432–8438
Anichtchik OV, Peitsaro N, Rinne JO, Kalimo H, Panula P (2001) Distribution and modulation of histamine H(3) receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson’s disease. Neurobiol Dis 8:707–716
Antonini A, Odin P (2009) Pros and cons of apomorphine and l-dopa continuous infusion in advanced Parkinson’s disease. Parkinsonism Relat Disord 15(Suppl 4):S97–S100
Antonini A, Ursino G, Calandrella D, Bernardi L, Plebani M (2010) Continuous dopaminergic delivery in Parkinson’s disease. J Neurol 257(Suppl 2):S305–S308
Anwyl R (1999) Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev 29(1):83–120
Anwyl R (2009) Metabotropic glutamate receptor-dependent long-term potentiation. Neuropharmacology 56(4):735–740
Arai R, Karasawa N, Geffard M, Nagatsu T, Nagatsu I (1994) Immunohistochemical evidence that central serotonin neurons produce dopamine from exogenous l-DOPA in the rat, with reference to the involvement of aromatic l-amino acid decarboxylase. Brain Res 667(2):295–299
Arai R, Karasawa N, Geffard M, Nagatsu I (1995) l-DOPA is converted to dopamine in serotonergic fibers of the striatum of the rat: a double-labeling immunofluorescence study. Neurosci Lett 195(3):195–198
Archer T, Fredriksson A (2003) An antihypokinesic action of alpha2-adrenoceptors upon MPTP-induced behaviour deficits in mice. J Neural Transm 110(2):183–200
Ariano MA (1983) Distribution of components of the guanosine 3′,5′-phosphate system in rat caudate-putamen. Neuroscience 10(3):707–723
Arias-Montano JA, Floran B, Garcia M, Aceves J, Young JM (2001) Histamine H(3) receptor-mediated inhibition of depolarization-induced, dopamine D(1) receptor-dependent release of [(3)H]-gamma-aminobutyric acid from rat striatal slices. Br J Pharmacol 133:165–171
Arrang JM, Garbarg M, Schwartz JC (1983) Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302:832–837
Arrang JM, Garbarg M, Lancelot JC, Lecomte JM, Pollard H, Robba M, Schunack W, Schwartz JC (1987) Highly potent and selective ligands for histamine H3-receptors. Nature 327:117–123
Ashton JC, Darlington CL, Smith PF (2006) Co-distribution of the cannabinoid CB1 receptor and the 5-HT transporter in the rat amygdale. Eur J Pharmacol 537(1–3):70–71
Aston-Jones G, Harris GC (2004) Brain substrates for increased drug seeking during protracted withdrawal. Neuropharmacology 47(Suppl 1):167–179
Aubert I, Guigoni C, Hakansson K, Li Q, Dovero S, Barthe N, Bioulac BH, Gross CE, Fisone G, Bloch B, Bezard E (2005) Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. Ann Neurol 57(1):17–26
Ballard PA, Tetrud JW, Langston JW (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. Neurology 35(7):949–956
Baptista T, Lopez ME, Teneud L, Contreras Q, Alastre T, de Quijada M, Araujo de Baptista E, Alternus M, Weiss SR, Musseo E, Paez X, Hernandez L (1997) Amantadine in the treatment of neuroleptic-induced obesity in rats: behavioral, endocrine and neurochemical correlates. Pharmacopsychiatry 30(2):43–54
Bara-Jimenez W, Sherzai A, Dimitrova T, Favit A, Bibbiani F, Gillespie M, Morris MJ, Mouradian MM, Chase TN (2003) Adenosine A(2A) receptor antagonist treatment of Parkinson’s disease. Neurology 61(3):293–296
Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38(8):1083–1152
Bateup HS, Santini E, Shen W, Birnbaum S, Valjent E, Surmeier DJ, Fisone G, Nestler EJ, Greengard P (2010) Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors. Proc Natl Acad Sci USA 107(33):14845–14850
Becker PM, Jamieson AO, Brown WD (1993) Dopaminergic agents in restless legs syndrome and periodic limb movements of sleep: response and complications of extended treatment in 49 cases. Sleep 16:713–716
Bellone C, Luscher C, Mameli M (2008) Mechanisms of synaptic depression triggered by metabotropic glutamate receptors. Cell Mol Life Sci 65(18):2913–2923
Belujon P, Lodge DJ, Grace AA (2010) Aberrant striatal plasticity is specifically associated with dyskinesia following levodopa treatment. Mov Disord 25(11):1568–1576
Bernard V, Gardiol A, Faucheux B, Bloch B, Agid Y, Hirsch EC (1996) Expression of glutamate receptors in the human and rat basal ganglia: effect of the dopaminergic denervation on AMPA receptor gene expression in the striatopallidal complex in Parkinson’s disease and rat with 6-OHDA lesion. J Comp Neurol 368(4):553–568
Besson MJ, Graybiel AM, Nastuk MA (1988) [3H]SCH 23390 binding to D1 dopamine receptors in the basal ganglia of the cat and primate: delineation of striosomal compartments and pallidal and nigral subdivisions. Neuroscience 26(1):101–119
Betarbet R, Porter RH, Greenamyre JT (2000) GluR1 glutamate receptor subunit is regulated differentially in the primate basal ganglia following nigrostriatal dopamine denervation. J Neurochem 74(3):1166–1174
Bezard E, Brotchie JM, Gross CE (2001) Pathophysiology of levodopa-induced dyskinesia: potential for new therapies. Nat Rev Neurosci 2(8):577–588
Bezard E, Hill MP, Crossman AR, Brotchie JM, Michel A, Grimee R, Klitgaard H (2004) Levetiracetam improves choreic levodopa-induced dyskinesia in the MPTP-treated macaque. Eur J Pharmacol 485:159–164
Bibbiani F, Oh JD, Chase TN (2001) Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology 57(10):1829–1834
Bibbiani F, Oh JD, Petzer JP, Castagnoli N Jr, Chen JF, Schwarzschild MA, Chase TN (2003) A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease. Exp Neurol 184(1):285–294
Bibbiani F, Oh JD, Kielaite A, Collins MA, Smith C, Chase TN (2005) Combined blockade of AMPA and NMDA glutamate receptors reduces levodopa-induced motor complications in animal models of PD. Exp Neurol 196(2):422–429
Bishop C, Taylor JL, Kuhn DM, Eskow KL, Park JY, Walker PD (2006) MDMA and fenfluramine reduce l-DOPA-induced dyskinesia via indirect 5-HT1A receptor stimulation. Eur J Neurosci 23(10):2669–2676
Bjorklund T, Carlsson T, Cederfjall EA, Carta M, Kirik D (2010) Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson’s disease. Brain 133(Pt 2):496–511
Blanchet PJ, Gomez-Mancilla B, Bedard PJ (1995) DOPA-induced “peak dose” dyskinesia: clues implicating D2 receptor-mediated mechanisms using dopaminergic agonists in MPTP monkeys. J Neural Transm Suppl 45:103–112
Blanchet PJ, Grondin R, Bedard PJ, Shiosaki K, Britton DR (1996) Dopamine D1 receptor desensitization profile in MPTP-lesioned primates. Eur J Pharmacol 309(1):13–20
Blanchet PJ, Konitsiotis S, Chase TN (1998) Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. Mov Disord 13(5):798–802
Blanchet PJ, Konitsiotis S, Whittemore ER, Zhou ZL, Woodward RM, Chase TN (1999) Differing effects of N-methyl-d-aspartate receptor subtype selective antagonists on dyskinesias in levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine monkeys. J Pharmacol Exp Ther 290(3):1034–1040
Blanchet PJ, Metman LV, Chase TN (2003) Renaissance of amantadine in the treatment of Parkinson’s disease. Adv Neurol 91:251–257
Bockelmann R, Wolf G, Ransmayr G, Riederer P (1994) NADPH-diaphorase/nitric oxide synthase containing neurons in normal and Parkinson’s disease putamen. J Neural Transm Park Dis Dement Sect 7(2):115–121
Bolam JP, Powell JF, Wu JY, Smith AD (1985) Glutamate decarboxylase-immunoreactive structures in the rat neostriatum: a correlated light and electron microscopic study including a combination of Golgi impregnation with immunocytochemistry. J Comp Neurol 237:1–20
Bonifati V, Fabrizio E, Cipriani R, Vanacore N, Meco G (1994) Buspirone in levodopa-induced dyskinesias. Clin Neuropharmacol 17(1):73–82
Boraud T, Bezard E, Bioulac B, Gross CE (2001) Dopamine agonist-induced dyskinesias are correlated to both firing pattern and frequency alterations of pallidal neurones in the MPTP-treated monkey. Brain 124(Pt 3):546–557
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(1):3–7
Boyce S, Rupniak NM, Steventon MJ, Iversen SD (1990b) Nigrostriatal damage is required for induction of dyskinesias by l-DOPA in squirrel monkeys. Clin Neuropharmacol 13(5):448–458
Breysse N, Baunez C, Spooren W, Gasparini F, Amalric M (2002) Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism. J Neurosci 22(13):5669–5678
Brodsky MA, Park BS, Nutt JG (2010) Effects of a dopamine agonist on the pharmacodynamics of levodopa in Parkinson disease. Arch Neurol 67(1):27–32
Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, Horak FB, Okun MS, Foote KD, Krack P, Pahwa R, Henderson JM, Hariz MI, Bakay RA, Rezai A, Marks WJ Jr, Moro E, Vitek JL, Weaver FM, Gross RE, DeLong MR (2011) Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch Neurol 68:165
Brooks DJ, Ibanez V, Sawle GV, Playford ED, Quinn N, Mathias CJ, Lees AJ, Marsden CD, Bannister R, Frackowiak RS (1992) Striatal D2 receptor status in patients with Parkinson’s disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography. Ann Neurol 31(2):184–192
Brooks DJ, Papapetropoulos S, Vandenhende F, Tomic D, He P, Coppell A, O’Neill G (2010) An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers. Clin Neuropharmacol 33(2):55–60
Brotchie JM (1998) Adjuncts to dopamine replacement: a pragmatic approach to reducing the problem of dyskinesia in Parkinson’s disease. Mov Disord 13(6):871–876
Brown TM, Brotchie JM, Fitzjohn SM (2003) Cannabinoids decrease corticostriatal synaptic transmission via an effect on glutamate uptake. J Neurosci 23(35):11073–11077
Brusco A, Tagliaferro P, Saez T, Onaivi ES (2008) Postsynaptic localization of CB2 cannabinoid receptors in the rat hippocampus. Synapse 62(12):944–949
Bucheler MM, Hadamek K, Hein L (2002) Two alpha(2)-adrenergic receptor subtypes, alpha(2A) and alpha(2C), inhibit transmitter release in the brain of gene-targeted mice. Neuroscience 109(4):819–826
Buck K, Ferger B (2010) The selective alpha1 adrenoceptor antagonist HEAT reduces l-DOPA-induced dyskinesia in a rat model of Parkinson’s disease. Synapse 64(2):117–126
Buck K, Voehringer P, Ferger B (2010a) Site-specific action of l-3,4-dihydroxyphenylalanine in the striatum but not globus pallidus and substantia nigra pars reticulata evokes dyskinetic movements in chronic l-3,4-dihydroxyphenylalanine-treated 6-hydroxydopamine-lesioned rats. Neuroscience 166(2):355–358
Buck K, Voehringer P, Ferger B (2010b) The alpha(2) adrenoceptor antagonist idazoxan alleviates l-DOPA-induced dyskinesia by reduction of striatal dopamine levels: an in vivo microdialysis study in 6-hydroxydopamine-lesioned rats. J Neurochem 112(2):444–452
Calabresi P, Maj R, Mercuri NB, Bernardi G (1992a) Coactivation of D1 and D2 dopamine receptors is required for long-term synaptic depression in the striatum. Neurosci Lett 142(1):95–99
Calabresi P, Maj R, Pisani A, Mercuri NB, Bernardi G (1992b) Long-term synaptic depression in the striatum: physiological and pharmacological characterization. J Neurosci 12(11):4224–4233
Calabresi P, Giacomini P, Centonze D, Bernardi G (2000a) Levodopa-induced dyskinesia: a pathological form of striatal synaptic plasticity? Ann Neurol 47(4 Suppl 1):S60–S68 discussion S68–69
Calabresi P, Gubellini P, Centonze D, Picconi B, Bernardi G, Chergui K, Svenningsson P, Fienberg AA, Greengard P (2000b) Dopamine and cAMP-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity. J Neurosci 20(22):8443–8451
Calabresi P, Di Filippo M, Ghiglieri V, Picconi B (2008) Molecular mechanisms underlying levodopa-induced dyskinesia. Mov Disord 23(Suppl 3):S570–S579
Callado LF, Hopwood SE, Hancock PJ, Stamford JA (2000) Effects of dizocilpine (MK 801) on noradrenaline, serotonin and dopamine release and uptake. Neuroreport 11(1):173–176
Canals M, Marcellino D, Fanelli F, Ciruela F, de Benedetti P, Goldberg SR, Neve K, Fuxe K, Agnati LF, Woods AS, Ferre S, Lluis C, Bouvier M, Franco R (2003) Adenosine A2A-dopamine D2 receptor-receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 278(47):46741–46749
Cao X, Liang L, Hadcock JR, Iredale PA, Griffith DA, Menniti FS, Factor S, Greenamyre JT, Papa SM (2007) 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 323(1):318–326
Carta M, Carlsson T, Kirik D, Bjorklund A (2007) Dopamine released from 5-HT terminals is the cause of l-DOPA-induced dyskinesia in parkinsonian rats. Brain 130(Pt 7):1819–1833
Cathala L, Guyon A, Eugene D, Paupardin-Tritsch D (2002) Alpha2-adrenoceptor activation increases a cationic conductance and spontaneous GABAergic synaptic activity in dopaminergic neurones of the rat substantia nigra. Neuroscience 115(4):1059–1065
Cenci MA, Lundblad M (2006) Post- versus presynaptic plasticity in l-DOPA-induced dyskinesia. J Neurochem 99(2):381–392
Cenci MA, Ohlin KE (2009) Rodent models of treatment-induced motor complications in Parkinson’s disease. Parkinsonism Relat Disord 15(Suppl 4):S13–S17
Cenci MA, Lee CS, Bjorklund 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(8):2694–2706
Centonze D, Grande C, Usiello A, Gubellini P, Erbs E, Martin AB, Pisani A, Tognazzi N, Bernardi G, Moratalla R, Borrelli E, Calabresi P (2003) Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons. J Neurosci 23(15):6245–6254
Chalimoniuk M, Langfort J (2007) The effect of subchronic, intermittent l-DOPA treatment on neuronal nitric oxide synthase and soluble guanylyl cyclase expression and activity in the striatum and midbrain of normal and MPTP-treated mice. Neurochem Int 50(6):821–833
Chaperon F, Thiebot MH (1999) Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol 13(3):243–281
Chase TN, Oh JD, Konitsiotis S (2000) Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms. J Neurol 247(Suppl 2):II36–II42
Chase TN, Bibbiani F, Bara-Jimenez W, Dimitrova T, Oh-Lee JD (2003) Translating A2A antagonist KW6002 from animal models to parkinsonian patients. Neurology 61(11 Suppl 6):S107–S111
Chen Q, Reiner A (1996) Cellular distribution of the NMDA receptor NR2A/2B subunits in the rat striatum. Brain Res 743(1–2):346–352
Clapham J, Kilpatrick GJ (1994) Thioperamide, the selective histamine H3 receptor antagonist, attenuates stimulant-induced locomotor activity in the mouse. Eur J Pharmacol 259:107–114
Collingridge GL, Singer W (1990) Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol Sci 11(7):290–296
Conn PJ, Battaglia G, Marino MJ, Nicoletti F (2005) Metabotropic glutamate receptors in the basal ganglia motor circuit. Nat Rev Neurosci 6:787–798
Contin M, Martinelli P (2010) Pharmacokinetics of levodopa. J Neurol 257:S253–S261
Corvol JC, Studler JM, Schonn JS, Girault JA, Herve D (2001) Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum. J Neurochem 76(5):1585–1588
Cotzias GC, Papavasiliou PS, Tolosa ES, Mendez JS, Bell-Midura M (1976) Treatment of Parkinson’s disease with aporphines. Possible role of growth hormone. N Engl J Med 294(11):567–572
Cox H, Togasaki DM, Chen L, Langston JW, Di Monte DA, Quik M (2007) The selective kappa-opioid receptor agonist U50, 488 reduces l-dopa-induced dyskinesias but worsens parkinsonism in MPTP-treated primates. Exp Neurol 205(1):101–107
Crossman AR (2000) Functional anatomy of movement disorders. J Anat 196(Pt 4):519–525
Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991) Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88(17):7797–7801
de la Fuente-Fernandez R, Sossi V, Huang Z, Furtado S, Lu JQ, Calne DB, Ruth TJ, Stoessl AJ (2004) Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias. Brain 127(Pt 12):2747–2754
Dekundy A, Pietraszek M, Schaefer D, Cenci MA, Danysz W (2006) Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson’s disease. Brain Res Bull 69:318–326
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(1):76–89
DeLong MR, Wichmann T (2007) Circuits and circuit disorders of the basal ganglia. Arch Neurol 64:20–24
Di Marzo V, Breivogel CS, Tao Q, Bridgen DT, Razdan RK, Zimmer AM, Zimmer A, Martin BR (2000) Levels, metabolism, and pharmacological activity of anandamide in CB(1) cannabinoid receptor knockout mice: evidence for non-CB(1), non-CB(2) receptor-mediated actions of anandamide in mouse brain. J Neurochem 75(6):2434–2444
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):459–466
Dreyer JK, Herrik KF, Berg RW, Hounsgaard JD (2010) Influence of phasic and tonic dopamine release on receptor activation. J Neurosci 30:14273–14283
Dugast C, Souliere F, Schmitt P, Casanovas JM, Fattaccini CM, Mocaer E, Lesourd M, Renaud B, Artigas F, Hamon M, Chouvet G (1998) Is the potent 5-HT1A receptor agonist, alnespirone (S-20499), affecting dopaminergic systems in the rat brain? Eur J Pharmacol 350(2–3):171–180
Duncan GE, Miyamoto S, Leipzig JN, Lieberman JA (2000) Comparison of the effects of clozapine, risperidone, and olanzapine on ketamine-induced alterations in regional brain metabolism. J Pharmacol Exp Ther 293(1):8–14
Durif F (1999) Treating and preventing levodopa-induced dyskinesias: current and future strategies. Drugs Aging 14(5):337–345
Durif F, Vidailhet M, Assal F, Roche C, Bonnet AM, Agid Y (1997) Low-dose clozapine improves dyskinesias in Parkinson’s disease. Neurology 48(3):658–662
Eve DJ, Nisbet AP, Kingsbury AE, Hewson EL, Daniel SE, Lees AJ, Marsden CD, Foster OJ (1998) Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson’s disease. Brain Res Mol Brain Res 63(1):62–71
Fabbrini G, Mouradian MM, Juncos JL, Schlegel J, Mohr E, Chase TN (1988) Motor fluctuations in Parkinson’s disease: central pathophysiological mechanisms, Part I. Ann Neurol 24:366–371
Fabbrini G, Brotchie JM, Grandas F, Nomoto M, Goetz CG (2007) Levodopa-induced dyskinesias. Mov Disord 22(10):1379–1389
Fahn S (2008) How do you treat motor complications in Parkinson’s disease: medicine, surgery, or both? Ann Neurol 64(Suppl 2):S56–S64
Fernandez-Espejo E, Caraballo I, Rodriguez de Fonseca F, Ferrer B, El Banoua F, Flores JA, Galan-Rodriguez B (2004) Experimental parkinsonism alters anandamide precursor synthesis, and functional deficits are improved by AM404: a modulator of endocannabinoid function. Neuropsychopharmacology 29(6):1134–1142
Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res 326(2):483–504
Ferre S, Fredholm BB, Morelli M, Popoli P, Fuxe K (1997) Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 20(10):482–487
Ferre S, Karcz-Kubicha M, Hope BT, Popoli P, Burgueno J, Gutierrez MA, Casado V, Fuxe K, Goldberg SR, Lluis C, Franco R, Ciruela F (2002) Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc Natl Acad Sci USA 99(18):11940–11945
Ferre S, Lluis C, Justinova Z, Quiroz C, Orru M, Navarro G, Canela EI, Franco R, Goldberg SR (2010) Adenosine-cannabinoid receptor interactions. Implications for striatal function. Br J Pharmacol 160(3):443–453
Ferrer B, Asbrock N, Kathuria S, Piomelli D, Giuffrida A (2003) Effects of levodopa on endocannabinoid levels in rat basal ganglia: implications for the treatment of levodopa-induced dyskinesias. Eur J Neurosci 18(6):1607–1614
Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Brain Res Mol Brain Res 14(3):186–195
Fiorentini C, Gardoni F, Spano P, Di Luca M, Missale C (2003) Regulation of dopamine D1 receptor trafficking and desensitization by oligomerization with glutamate N-methyl-d-aspartate receptors. J Biol Chem 278(22):20196–20202
Fiorentini C, Rizzetti MC, Busi C, Bontempi S, Collo G, Spano P, Missale C (2006) Loss of synaptic D1 dopamine/N-methyl-d-aspartate glutamate receptor complexes in l-DOPA-induced dyskinesia in the rat. Mol Pharmacol 69(3):805–812
Fiorentini C, Busi C, Gorruso E, Gotti C, Spano P, Missale C (2008) Reciprocal regulation of dopamine D1 and D3 receptor function and trafficking by heterodimerization. Mol Pharmacol 74(1):59–69
Fleckenstein AE, Lookingland KJ, Moore KE (1993) Activation of mesolimbic dopaminergic neurons following central administration of histamine is mediated by H1 receptors. Naunyn Schmiedebergs Arch Pharmacol 347:50–54
Fleckenstein AE, Volz TJ, Hanson GR (2009) Psychostimulant-induced alterations in vesicular monoamine transporter-2 function: neurotoxic and therapeutic implications. Neuropharmacology 56(Suppl 1):133–138
Fox SH, Henry B, Hill M, Crossman A, Brotchie J (2002) Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson’s disease. Mov Disord 17(6):1180–1187
Fox SH, Chuang R, Brotchie JM (2009) Serotonin and Parkinson’s disease: on movement, mood, and madness. Mov Disord 24(9):1255–1266
Frechilla D, Cobreros A, Saldise L, Moratalla R, Insausti R, Luquin M, Del Rio J (2001) Serotonin 5-HT(1A) receptor expression is selectively enhanced in the striosomal compartment of chronic parkinsonian monkeys. Synapse 39(4):288–296
Fredduzzi S, Moratalla R, Monopoli A, Cuellar B, Xu K, Ongini E, Impagnatiello F, Schwarzschild MA, Chen JF (2002) Persistent behavioral sensitization to chronic l-DOPA requires A2A adenosine receptors. J Neurosci 22(3):1054–1062
Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 344(10):710–719
Freeman A, Ciliax B, Bakay R, Daley J, Miller RD, Keating G, Levey A, Rye D (2001) Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models. Ann Neurol 50:321–329
Fusco FR, Martorana A, Giampa C, De March Z, Farini D, D’Angelo V, Sancesario G, Bernardi G (2004) Immunolocalization of CB1 receptor in rat striatal neurons: a confocal microscopy study. Synapse 53(3):159–167
Fuxe K, Ferre S, Genedani S, Franco R, Agnati LF (2007) Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function. Physiol Behav 92(1–2):210–217
Gaikwad RV, Gaonkar RK, Jadhav SA, Thorat VM, Jadhav JH, Balsara JJ (2005) Involvement of central serotonergic systems in dextromethorphan-induced behavioural syndrome in rats. Indian J Exp Biol 43(7):620–625
Gardoni F, Picconi B, Ghiglieri V, Polli F, Bagetta V, Bernardi G, Cattabeni F, Di Luca M, Calabresi P (2006) A critical interaction between NR2B and MAGUK in l-DOPA induced dyskinesia. J Neurosci 26(11):2914–2922
Garthwaite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336(6197):385–388
Gaspar P, Febvret A, Colombo J (1993) Serotonergic sprouting in primate MTP-induced hemiparkinsonism. Exp Brain Res 96(1):100–106
Gerdeman G, Lovinger DM (2001) CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. J Neurophysiol 85(1):468–471
Gerfen CR (1992) The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. Annu Rev Neurosci 15:285–320
Gerfen CR (2003) D1 dopamine receptor supersensitivity in the dopamine-depleted striatum animal model of Parkinson’s disease. Neuroscientist 9(6):455–462
Gerfen CR, Engber TM (1992) Molecular neuroanatomic mechanisms of Parkinson’s disease: a proposed therapeutic approach. Neurol Clin 10(2):435–449
Gerfen CR, Surmeier DJ (2011) Modulation of striatal projection systems by dopamine. Annu Rev Neurosci 34:441–66
Gerlach M, Oehler D, Blum-Degen D, Lange KW, Mayer B, Reichmann H, Riederer P (1995) Regional distribution and characterization of nitric oxide synthase activity in the brain of the common marmoset. Neuroreport 6(8):1141–1145
Gilgun-Sherki Y, Melamed E, Mechoulam R, Offen D (2003) The CB1 cannabinoid receptor agonist, HU-210, reduces levodopa-induced rotations in 6-hydroxydopamine-lesioned rats. Pharmacol Toxicol 93(2):66–70
Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2(4):358–363
Gobert A, Lejeune F, Rivet JM, Audinot V, Newman-Tancredi A, Millan MJ (1995) Modulation of the activity of central serotoninergic neurons by novel serotonin1A receptor agonists and antagonists: a comparison to adrenergic and dopaminergic neurons in rats. J Pharmacol Exp Ther 273(3):1032–1046
Goetz CG, Damier P, Hicking C, Laska E, Muller T, Olanow CW, Rascol O, Russ H (2007) Sarizotan as a treatment for dyskinesias in Parkinson’s disease: a double-blind placebo-controlled trial. Mov Disord 22:179–186
Gomes MZ, Del Bel EA (2003) Effects of electrolytic and 6-hydroxydopamine lesions of rat nigrostriatal pathway on nitric oxide synthase and nicotinamide adenine dinucleotide phosphate diaphorase. Brain Res Bull 62(2):107–115
Gomez-Mancilla B, Bedard PJ (1993) Effect of nondopaminergic drugs on l-dopa-induced dyskinesias in MPTP-treated monkeys. Clin Neuropharmacol 16(5):418–427
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 21:839–846
Gong JP, Onaivi ES, Ishiguro H, Liu QR, Tagliaferro PA, Brusco A, Uhl GR (2006) Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res 1071(1):10–23
Goodchild RE, Court JA, Hobson I, Piggott MA, Perry RH, Ince P, Jaros E, Perry EK (1999) Distribution of histamine H3-receptor binding in the normal human basal ganglia: comparison with Huntington’s and Parkinson’s disease cases. Eur J Neurosci 11:449–456
Goulet M, Grondin R, Blanchet PJ, Bedard PJ, Di Paolo T (1996) Dyskinesias and tolerance induced by chronic treatment with a D1 agonist administered in pulsatile or continuous mode do not correlate with changes of putaminal D1 receptors in drug-naive MPTP monkeys. Brain Res 719(1–2):129–137
Goulet M, Grondin R, Morissette M, Maltais S, Falardeau P, Bedard PJ, Di Paolo T (2000) Regulation by chronic treatment with cabergoline of dopamine D1 and D2 receptor levels and their expression in the striatum of Parkinsonian-monkeys. Prog Neuropsychopharmacol Biol Psychiatry 24(4):607–617
Graham WC, Sambrook MA, Crossman AR (1993) Differential effect of chronic dopaminergic treatment on dopamine D1 and D2 receptors in the monkey brain in MPTP-induced parkinsonism. Brain Res 602:290–303
Greengard P, Allen PB, Nairn AC (1999) Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 23(3):435–447
Grenhoff J, Nisell M, Ferre S, Aston-Jones G, Svensson TH (1993) Noradrenergic modulation of midbrain dopamine cell firing elicited by stimulation of the locus coeruleus in the rat. J Neural Transm Gen Sect 93(1):11–25
Grenhoff J, North RA, Johnson SW (1995) Alpha 1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice. Eur J Neurosci 7(8):1707–1713
Grondin R, Bedard PJ, Hadj Tahar A, Gregoire L, Mori A, Kase H (1999) Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 52(8):1673–1677
Grondin R, Hadj Tahar A, Doan VD, Ladure P, Bedard PJ (2000) Noradrenoceptor antagonism with idazoxan improves l-dopa-induced dyskinesias in MPTP monkeys. Naunyn Schmiedebergs Arch Pharmacol 361(2):181–186
Guan XM, McBride WJ (1989) Serotonin microinfusion into the ventral tegmental area increases accumbens dopamine release. Brain Res Bull 23(6):541–547
Guevara-Guzman R, Emson PC, Kendrick KM (1994) Modulation of in vivo striatal transmitter release by nitric oxide and cyclic GMP. J Neurochem 62(2):807–810
Guigoni C, Dovero S, Aubert I, Li Q, Bioulac BH, Bloch B, Gurevich EV, Gross CE, Bezard E (2005) Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial lesioning. Eur J Neurosci 22(1):283–287
Gurd JW (1997) Protein tyrosine phosphorylation: implications for synaptic function. Neurochem Int 31(5):635–649
Guttenberg ND, Klop H, Minami M, Satoh M, Voorn P (1996) Co-localization of mu opioid receptor is greater with dynorphin than enkephalin in rat striatum. Neuroreport 7(13):2119–2124
Guttman M, Seeman P (1985) l-dopa reverses the elevated density of D2 dopamine receptors in Parkinson’s diseased striatum. J Neural Transm 64:93–103
Hadj Tahar A, Belanger N, Bangassoro E, Gregoire L, Bedard PJ (2000) Antidyskinetic effect of JL-18, a clozapine analog, in parkinsonian monkeys. Eur J Pharmacol 399(2–3):183–186
Hadj Tahar A, Gregoire L, Darre A, Belanger N, Meltzer L, Bedard PJ (2004) Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys. Neurobiol Dis 15(2):171–176
Hagell P, Piccini P, Bjorklund A, Brundin P, Rehncrona S, Widner H, Crabb L, Pavese N, Oertel WH, Quinn N, Brooks DJ, Lindvall O (2002) Dyskinesias following neural transplantation in Parkinson’s disease. Nat Neurosci 5(7):627–628
Hametner E, Seppi K, Poewe W (2010) The clinical spectrum of levodopa-induced motor complications. J Neurol 257:S268–S275
Hauser RA, Shulman LM, Trugman JM, Roberts JW, Mori A, Ballerini R, Sussman NM (2008) Study of istradefylline in patients with Parkinson’s disease on levodopa with motor fluctuations. Mov Disord 23(15):2177–2185
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(2):334–342
Henry B, Fox SH, Crossman AR, Brotchie JM (2001) Mu- and delta-opioid receptor antagonists reduce levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson’s disease. Exp Neurol 171(1):139–146
Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87(5):1932–1936
Herkenham M, Lynn AB, de Costa BR, Richfield EK (1991a) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547(2):267–274
Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991b) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11(2):563–583
Hidaka S, Totterdell S (2001) Ultrastructural features of the nitric oxide synthase-containing interneurons in the nucleus accumbens and their relationship with tyrosine hydroxylase-containing terminals. J Comp Neurol 431(2):139–154
Hill SJ (2006) G-protein-coupled receptors: past, present and future. Br J Pharmacol 147(Suppl 1):S27–S37
Hill MP, Bezard E, McGuire SG, Crossman AR, Brotchie JM, Michel A, Grimee R, Klitgaard H (2003) Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by l-dopa and ropinirole in the MPTP-lesioned marmoset. Mov Disord 18:1301–1305
Hill MP, Ravenscroft P, Bezard E, Crossman AR, Brotchie JM, Michel A, Grimee R, Klitgaard H (2004) Levetiracetam potentiates the antidyskinetic action of amantadine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson’s disease. J Pharmacol Exp Ther 310(1):386–394
Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, Hansson A, Watson S, Olah ME, Mallol J, Canela EI, Zoli M, Agnati LF, Ibanez CF, Lluis C, Franco R, Ferre S, Fuxe K (2002) Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 277(20):18091–18097
Hisatsune C, Umemori H, Inoue T, Michikawa T, Kohda K, Mikoshiba K, Yamamoto T (1997) Phosphorylation-dependent regulation of N-methyl-d-aspartate receptors by calmodulin. J Biol Chem 272(33):20805–20810
Hjorth S, Magnusson T (1988) The 5-HT 1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo. Naunyn Schmiedebergs Arch Pharmacol 338(5):463–471
Hollister AS, Breese GR, Mueller RA (1979) Role of monoamine neural systems in l-dihydroxyphenylalanine-stimulated activity. J Pharmacol Exp Ther 208(1):37–43
Holmberg M, Scheinin M, Kurose H, Miettinen R (1999) Adrenergic alpha2C-receptors reside in rat striatal GABAergic projection neurons: comparison of radioligand binding and immunohistochemistry. Neuroscience 93(4):1323–1333
Honrubia MA, Vilaro MT, Palacios JM, Mengod G (2000) Distribution of the histamine H(2) receptor in monkey brain and its mRNA localization in monkey and human brain. Synapse 38:343–354
Huot P, Johnston TH, Koprich JB, Winkelmolen L, Fox SH, Brotchie JM (2011) Regulation of cortical and striatal 5-HT(1A) receptors in the MPTP-lesioned macaque. Neurobiol Aging (Epub ahead of print)
Hurley MJ, Jenner P (2006) What has been learnt from study of dopamine receptors in Parkinson’s disease? Pharmacol Ther 111(3):715–728
Hurley MJ, Mash DC, Jenner P (2003) Expression of cannabinoid CB1 receptor mRNA in basal ganglia of normal and parkinsonian human brain. J Neural Transm 110(11):1279–1288
Hurley MJ, Jackson MJ, Smith LA, Rose S, Jenner P (2005) Immunoautoradiographic analysis of NMDA receptor subunits and associated postsynaptic density proteins in the brain of dyskinetic MPTP-treated common marmosets. Eur J Neurosci 21(12):3240–3250
Iravani MM, Millar J, Kruk ZL (1998) Differential release of dopamine by nitric oxide in subregions of rat caudate putamen slices. J Neurochem 71(5):1969–1977
Iravani MM, Muscat R, Kruk ZL (1999) MK-801 interaction with the 5-HT transporter: a real-time study in brain slices using fast cyclic voltammetry. Synapse 32(3):212–224
Iravani MM, Costa S, Jackson MJ, Tel BC, Cannizzaro C, Pearce RK, Jenner P (2001) GDNF reverses priming for dyskinesia in MPTP-treated, l-DOPA-primed common marmosets. Eur J Neurosci 13(3):597–608
Iravani MM, Jackson MJ, Kuoppamaki M, Smith LA, Jenner P (2003) 3,4-methylenedioxymethamphetamine (ecstasy) inhibits dyskinesia expression and normalizes motor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates. J Neurosci 23(27):9107–9115
Iravani MM, Costa S, Al-Bargouthy G, Jackson MJ, Zeng BY, Kuoppamaki M, Obeso JA, Jenner P (2005) Unilateral pallidotomy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets exhibiting levodopa-induced dyskinesia. Eur J Neurosci 22(6):1305–1318
Iravani MM, Tayarani-Binazir K, Chu WB, Jackson MJ, Jenner P (2006) In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with increased motor disability. J Pharmacol Exp Ther 319(3):1225–1234
Iravani MM, Stockwell KA, Tayarani-Binazir K, Jackson MJ, Rose S, Jenner P (2008) Inhibition of neuronal nitric oxide synthase as a novel target for dyskinesia suppression in primates. Soc Neurosci Abstr 139.15/M6
Itokawa K, Ohkuma A, Araki N, Tamura N, Shimazu K (2006) Effect of l-DOPA on nitric oxide production in striatum of freely mobile mice. Neurosci Lett 402(1–2):142–144
Jackson MJ, Al-Barghouthy G, Pearce RK, Smith L, Hagan JJ, Jenner P (2004) Effect of 5-HT1B/D receptor agonist and antagonist administration on motor function in haloperidol and MPTP-treated common marmosets. Pharmacol Biochem Behav 79(3):391–400
Jackson MJ, Smith LA, Al-Barghouthy G, Rose S, Jenner P (2007) Decreased expression of l-dopa-induced dyskinesia by switching to ropinirole in MPTP-treated common marmosets. Exp Neurol 204(1):162–170
Jankovic J (2005) Motor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations. Mov Disord 20(Suppl 11):S11–S16
Jankovic J, Rajput AH, McDermott MP, Perl DP (2000) The evolution of diagnosis in early Parkinson disease. Parkinson Study Group. Arch Neurol 57:369–372
Jenner P (2003a) A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD. Neurology 61(11 Suppl 6):S32–S38
Jenner P (2003b) Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson’s disease. Curr Opin Neurol 16(Suppl 1):S3–S7
Jenner P (2008) Molecular mechanisms of l-DOPA-induced dyskinesia. Nat Rev Neurosci 9(9):665–677
Jenner P (2009) From the MPTP-treated primate to the treatment of motor complications in Parkinson’s disease. Parkinsonism Relat Disord 15(Suppl 4):S18–S23
Johnson EA, Tsai CE, Shahan YH, Azzaro AJ (1993) Serotonin 5-HT1A receptors mediate inhibition of tyrosine hydroxylation in rat striatum. J Pharmacol Exp Ther 266(1):133–141
Johnston TH, Fox SH, McIldowie MJ, Piggott MJ, Brotchie JM (2010a) Reduction of l-DOPA-induced dyskinesia by the selective metabotropic glutamate receptor 5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson’s disease. J Pharmacol Exp Ther 333(3):865–873
Johnston TH, van der Meij A, Brotchie JM, Fox SH (2010b) Effect of histamine H2 receptor antagonism on levodopa-induced dyskinesia in the MPTP-macaque model of Parkinson’s disease. Mov Disord 25:1379–1390
Kachroo A, Orlando LR, Grandy DK, Chen JF, Young AB, Schwarzschild MA (2005) Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice. J Neurosci 25(45):10414–10419
Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H, Kuwana Y, Jenner P (1998) Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 43(4):507–513
Kannari K, Yamato H, Shen H, Tomiyama M, Suda T, Matsunaga M (2001) Activation of 5-HT(1A) but not 5-HT(1B) receptors attenuates an increase in extracellular dopamine derived from exogenously administered l-DOPA in the striatum with nigrostriatal denervation. J Neurochem 76(5):1346–1353
Kannari K, Kurahashi K, Tomiyama M, Maeda T, Arai A, Baba M, Suda T, Matsunaga M (2002) Tandospirone citrate, a selective 5-HT1A agonist, alleviates l-DOPA-induced dyskinesia in patients with Parkinson’s disease. No To Shinkei 54(2):133–137
Karlsborg M, Korbo L, Regeur L, Glad A (2010) Duodopa pump treatment in patients with advanced Parkinson’s disease. Dan Med Bull 57:A4155
Kelsey JE, Harris O, Cassin J (2009) The CB(1) antagonist rimonabant is adjunctively therapeutic as well as monotherapeutic in an animal model of Parkinson’s disease. Behav Brain Res 203(2):304–307
Kendrick KM, Guevara-Guzman R, de la Riva C, Christensen J, Ostergaard K, Emson PC (1996) NMDA and kainate-evoked release of nitric oxide and classical transmitters in the rat striatum: in vivo evidence that nitric oxide may play a neuroprotective role. Eur J Neurosci 8(12):2619–2634
Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. Pathophysiologic and clinical implications. N Engl J Med 318:876–880
Kish SJ, Shannak K, Rajput A, Deck JH, Hornykiewicz O (1992) Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson’s disease. J Neurochem 58:642–648
Konitsiotis S, Blanchet PJ, Verhagen L, Lamers E, Chase TN (2000) AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology 54(8):1589–1595
Konradi C, Westin JE, Carta M, Eaton ME, Kuter K, Dekundy A, Lundblad M, Cenci MA (2004) Transcriptome analysis in a rat model of l-DOPA-induced dyskinesia. Neurobiol Dis 17(2):219–236
Kostrzewa RM, Nowak P, Kostrzewa JP, Kostrzewa RA, Brus R (2005) Peculiarities of l-DOPA treatment of Parkinson’s disease. Amino Acids 28:157–164
Kullmann DM, Asztely F (1998) Extrasynaptic glutamate spillover in the hippocampus: evidence and implications. Trends Neurosci 21(1):8–14
Kullmann DM, Lamsa K (2008) Roles of distinct glutamate receptors in induction of anti-Hebbian long-term potentiation. J Physiol 586(6):1481–1486
Kumar A, Mann S, Sossi V, Ruth TJ, Stoessl AJ, Schulzer M, Lee CS (2003) [11C]DTBZ-PET correlates of levodopa responses in asymmetric Parkinson’s disease. Brain 126(Pt 12):2648–2655
Lai SK, Tse YC, Yang MS, Wong CK, Chan YS, Yung KK (2003) Gene expression of glutamate receptors GluR1 and NR1 is differentially modulated in striatal neurons in rats after 6-hydroxydopamine lesion. Neurochem Int 43(7):639–653
Lang AE, Lozano A, Montgomery EB, Tasker RR, Hutchison WD (1999) Posteroventral medial pallidotomy in advanced Parkinson’s disease. Adv Neurol 80:575–583
Langston JW, Ballard P (1984) Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can J Neurol Sci 11(1 Suppl):160–165
Le Moine C, Bloch B (1995) D1 and D2 dopamine receptor gene expression in the rat striatum: sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal populations of the dorsal and ventral striatum. J Comp Neurol 355(3):418–426
Le Moine C, Kieffer B, Gaveriaux-Ruff C, Befort K, Bloch B (1994) Delta-opioid receptor gene expression in the mouse forebrain: localization in cholinergic neurons of the striatum. Neuroscience 62(3):635–640
Lebois EP, Jones CK, Lindsley CW (2011) The evolution of histamine H(3) antagonists/inverse agonists. Curr Top Med Chem
Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Bohme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283(5400):401–404
Levandis G, Bazzini E, Armentero MT, Nappi G, Blandini F (2008) Systemic administration of an mGluR5 antagonist, but not unilateral subthalamic lesion, counteracts l-DOPA-induced dyskinesias in a rodent model of Parkinson’s disease. Neurobiol Dis 29(1):161–168
LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM (2008) Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol 63(3):295–302
Li Y, Huang XF, Deng C, Meyer B, Wu A, Yu Y, Ying W, Yang GY, Yenari MA, Wang Q (2010) Alterations in 5-HT2A receptor binding in various brain regions among 6-hydroxydopamine-induced Parkinsonian rats. Synapse 64(3):224–230
Lin CW, Bianchi BR, Miller TR, Stashko MA, Wang SS, Curzon P, Bednarz L, Asin KE, Britton DR (1996) Persistent activation of the dopamine D1 receptor contributes to prolonged receptor desensitization: studies with A-77636. J Pharmacol Exp Ther 276:1022–1029
Linazasoro G (2005) New ideas on the origin of l-dopa-induced dyskinesias: age, genes and neural plasticity. Trends Pharmacol Sci 26:391–397
Linazasoro G, Van Blercom N, Bergaretxe A, Inaki FM, Laborda E, Ruiz Ortega JA (2009) Levodopa-induced dyskinesias in Parkinson disease are independent of the extent of striatal dopaminergic denervation: a pharmacological and SPECT study. Clin Neuropharmacol 32:326–329
Lindgren HS, Andersson DR, Lagerkvist S, Nissbrandt H, Cenci MA (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(6):1465–1476
Lindskog M, Svenningsson P, Fredholm B, Greengard P, Fisone G (1999) Mu- and delta-opioid receptor agonists inhibit DARPP-32 phosphorylation in distinct populations of striatal projection neurons. Eur J Neurosci 11(6):2182–2186
Liprando LA, Miner LH, Blakely RD, Lewis DA, Sesack SR (2004) Ultrastructural interactions between terminals expressing the norepinephrine transporter and dopamine neurons in the rat and monkey ventral tegmental area. Synapse 52(4):233–244
Liu F, Grauer S, Kelley C, Navarra R, Graf R, Zhang G, Atkinson PJ, Popiolek M, Wantuch C, Khawaja X, Smith D, Olsen M, Kouranova E, Lai M, Pruthi F, Pulicicchio C, Day M, Gilbert A, Pausch MH, Brandon NJ, Beyer CE, Comery TA, Logue S, Rosenzweig-Lipson S, Marquis KL (2008) ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piper idin-1-yl}-methanone]: a novel metabotropic glutamate receptor 5-selective positive allosteric modulator with preclinical antipsychotic-like and procognitive activities. J Pharmacol Exp Ther 327(3):827–839
Lorenc-Koci E, Wolfarth S (1999) Efficacy of pramipexole, a new dopamine receptor agonist, to relieve the parkinsonian-like muscle rigidity in rats. Eur J Pharmacol 385(1):39–46
Lundblad M, Andersson M, Winkler C, Kirik D, Wierup N, Cenci MA (2002) Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson’s disease. Eur J Neurosci 15(1):120–132
Lundblad M, Vaudano E, Cenci MA (2003) Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l-DOPA-induced dyskinesia. J Neurochem 84(6):1398–1410
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(1):110–123
Lundblad M, Usiello A, Carta M, Hakansson K, Fisone G, Cenci MA (2005) Pharmacological validation of a mouse model of l-dopa-induced dyskinesia. Exp Neurol 194(1):66–75
Lyons KE, Pahwa R (2006) Efficacy and tolerability of levetiracetam in Parkinson disease patients with levodopa-induced dyskinesia. Clin Neuropharmacol 29:148–153
MacDonald E, Kobilka BK, Scheinin M (1997) Gene targeting—homing in on alpha 2-adrenoceptor-subtype function. Trends Pharmacol Sci 18:211–219
Madeja M, Margineanu DG, Gorji A, Siep E, Boerrigter P, Klitgaard H, Speckmann EJ (2003) Reduction of voltage-operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action? Neuropharmacology 45:661–671
Maeda T, Kannari K, Shen H, Arai A, Tomiyama M, Matsunaga M, Suda T (2003) Rapid induction of serotonergic hyperinnervation in the adult rat striatum with extensive dopaminergic denervation. Neurosci Lett 343(1):17–20
Maeda T, Nagata K, Yoshida Y, Kannari K (2005) Serotonergic hyperinnervation into the dopaminergic denervated striatum compensates for dopamine conversion from exogenously administered l-DOPA. Brain Res 1046(1–2):230–233
Mannaioni G, Marino MJ, Valenti O, Traynelis SF, Conn PJ (2001) Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci 21(16):5925–5934
Manson AJ, Katzenschlager R, Hobart J, Lees AJ (2001) High dose naltrexone for dyskinesias induced by levodopa. J Neurol Neurosurg Psychiatry 70(4):554–556
Mansour A, Fox CA, Burke S, Meng F, Thompson RC, Akil H, Watson SJ (1994) Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study. J Comp Neurol 350(3):412–438
Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M (2010) Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol 9:413–424
Maratos EC, Jackson MJ, Pearce RK, Jenner P (2001) Antiparkinsonian activity and dyskinesia risk of ropinirole and l-DOPA combination therapy in drug naive MPTP-lesioned common marmosets (Callithrix jacchus). Mov Disord 16:631–641
Maratos EC, Jackson MJ, Pearce RK, Cannizzaro C, Jenner P (2003) Both short- and long-acting D-1/D-2 dopamine agonists induce less dyskinesia than l-DOPA in the MPTP-lesioned common marmoset (Callithrix jacchus). Exp Neurol 179(1):90–102
Marino MJ, Conn JP (2002) Modulation of the basal ganglia by metabotropic glutamate receptors: potential for novel therapeutics. Curr Drug Targets CNS Neurol Disord 1(3):239–250
Marino MJ, Awad H, Poisik O, Wittmann M, Conn PJ (2002) Localization and physiological roles of metabotropic glutamate receptors in the direct and indirect pathways of the basal ganglia. Amino Acids 23(1–3):185–191
Martin AB, Fernandez-Espejo E, Ferrer B, Gorriti MA, Bilbao A, Navarro M, Rodriguez de Fonseca F, Moratalla R (2008) Expression and function of CB1 receptor in the rat striatum: localization and effects on D1 and D2 dopamine receptor-mediated motor behaviors. Neuropsychopharmacology 33(7):1667–1679
Masukawa Y, Suzuki T, Misawa M (1993) Differential modification of the rewarding effects of methamphetamine and cocaine by opioids and antihistamines. Psychopharmacology (Berl) 111:139–143
Mazzucchelli C, Vantaggiato C, Ciamei A, Fasano S, Pakhotin P, Krezel W, Welzl H, Wolfer DP, Pages G, Valverde O, Marowsky A, Porrazzo A, Orban PC, Maldonado R, Ehrengruber MU, Cestari V, Lipp HP, Chapman PF, Pouyssegur J, Brambilla R (2002) Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory. Neuron 34(5):807–820
Meco G, Fabrizio E, Di Rezze S, Alessandri A, Pratesi L (2003) Mirtazapine in l-dopa-induced dyskinesias. Clin Neuropharmacol 26(4):179–181
Meco G, Stirpe P, Edito F, Purcaro C, Valente M, Bernardi S, Vanacore N (2009) Aripiprazole in l-dopa-induced dyskinesias: a one-year open-label pilot study. J Neural Transm 116:881–884
Melamed E, Hefti F, Wurtman RJ (1980a) Nonaminergic striatal neurons convert exogenous l-dopa to dopamine in parkinsonism. Ann Neurol 8:558–563
Melamed E, Hefti F, Wurtman RJ (1980b) Diminished decarboxylation of l-DOPA in rat striatum after intrastriatal injections of kainic acid. Neuropharmacology 19:409–411
Meurers BH, Dziewczapolski G, Shi T, Bittner A, Kamme F, Shults CW (2009) Dopamine depletion induces distinct compensatory gene expression changes in DARPP-32 signal transduction cascades of striatonigral and striatopallidal neurons. J Neurosci 29(21):6828–6839
Millan MJ, Di Cara B, Hill M, Jackson M, Joyce JN, Brotchie J, McGuire S, Crossman A, Smith L, Jenner P, Gobert A, Peglion JL, Brocco M (2004) S32504, a novel naphtoxazine agonist at dopamine D3/D2 receptors: II. Actions in rodent, primate, and cellular models of antiparkinsonian activity in comparison to ropinirole. J Pharmacol Exp Ther 309:921–935
Minami M, Satoh M (1995) Molecular biology of the opioid receptors: structures, functions and distributions. Neurosci Res 23(2):121–145
Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78(1):189–225
Molina-Hernandez A, Nunez A, Arias-Montano JA (2000) Histamine H3-receptor activation inhibits dopamine synthesis in rat striatum. Neuroreport 11:163–166
Molina-Hernandez A, Nunez A, Sierra JJ, Arias-Montano JA (2001) Histamine H3 receptor activation inhibits glutamate release from rat striatal synaptosomes. Neuropharmacology 41:928–934
Monory K, Blaudzun H, Massa F, Kaiser N, Lemberger T, Schutz G, Wotjak CT, Lutz B, Marsicano G (2007) Genetic dissection of behavioural and autonomic effects of Delta(9)-tetrahydrocannabinol in mice. PLoS Biol 5(10):e269
Morelli M, Di Chiara G (1987) Agonist-induced homologous and heterologous sensitization to D-1- and D-2-dependent contraversive turning. Eur J Pharmacol 141(1):101–107
Morelli M, Di Paolo T, Wardas J, Calon F, Xiao D, Schwarzschild MA (2007) Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. Prog Neurobiol 83(5):293–309
Morera-Herreras T, Ruiz-Ortega JA, Ugedo L (2010) Two opposite effects of Delta(9)-tetrahydrocannabinol on subthalamic nucleus neuron activity: involvement of GABAergic and glutamatergic neurotransmission. Synapse 64(1):20–29
Morgese MG, Cassano T, Cuomo V, Giuffrida A (2007) Anti-dyskinetic effects of cannabinoids in a rat model of Parkinson’s disease: role of CB(1) and TRPV1 receptors. Exp Neurol 208(1):110–119
Morgese MG, Cassano T, Gaetani S, Macheda T, Laconca L, Dipasquale P, Ferraro L, Antonelli T, Cuomo V, Giuffrida A (2009) Neurochemical changes in the striatum of dyskinetic rats after administration of the cannabinoid agonist WIN55, 212–2. Neurochem Int 54(1):56–64
Morin N, Gregoire L, Gomez-Mancilla B, Gasparini F, Di Paolo T (2010) Effect of the metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys. Neuropharmacology 58(7):981–986
Morissette M, Goulet M, Calon F, Falardeau P, Blanchet PJ, Bedard PJ, Di Paolo T (1996) Changes of D1 and D2 dopamine receptor mRNA in the brains of monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: correction with chronic administration of l-3,4-dihydroxyphenylalanine. Mol Pharmacol 50(5):1073–1079
Morissette M, Dridi M, Calon F, Hadj Tahar A, Meltzer LT, Bedard PJ, Di Paolo T (2006) Prevention of dyskinesia by an NMDA receptor antagonist in MPTP monkeys: effect on adenosine A2A receptors. Synapse 60(3):239–250
Mouradian MM, Juncos JL, Fabbrini G, Chase TN (1987) Motor fluctuations in Parkinson’s disease: pathogenetic and therapeutic studies. Ann Neurol 22(4):475–479
Muller DL, Unterwald EM (2004) In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine. J Pharmacol Exp Ther 310(2):774–782
Munoz A, Li Q, Gardoni F, Marcello E, Qin C, Carlsson T, Kirik D, Di Luca M, Bjorklund A, Bezard E, Carta M (2008) Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of l-DOPA-induced dyskinesia. Brain 131(Pt 12):3380–3394
Murata M (2010) Zonisamide: a new drug for Parkinson’s disease. Drugs Today (Barc) 46:251–258
Murer MG, Dziewczapolski G, Menalled LB, Garcia MC, Agid Y, Gershanik O, Raisman-Vozari R (1998) Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions. Ann Neurol 43:561–575
Murphy LO, Smith S, Chen RH, Fingar DC, Blenis J (2002) Molecular interpretation of ERK signal duration by immediate early gene products. Nat Cell Biol 4(8):556–564
Navailles S, Bioulac B, Gross C, De Deurwaerdere P (2010) Serotonergic neurons mediate ectopic release of dopamine induced by l-DOPA in a rat model of Parkinson’s disease. Neurobiol Dis 38(1):136–143
Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2(2):119–128
Neustadt BR, Hao J, Lindo N, Greenlee WJ, Stamford AW, Tulshian D, Ongini E, Hunter J, Monopoli A, Bertorelli R, Foster C, Arik L, Lachowicz J, Ng K, Feng KI (2007) Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines. Bioorg Med Chem Lett 17(5):1376–1380
Ng KY, Chase TN, Colburn RW, Kopin IJ (1970) l-Dopa-induced release of cerebral monoamines. Science 170(953):76–77
Ng KY, Colburn RW, Kopin IJ (1971) Effects of l-dopa on efflux of cerebral monoamines from synaptosomes. Nature 230(5292):331–332
Ng NK, Lee HS, Wong PT (1999) Regulation of striatal dopamine release through 5-HT1 and 5-HT2 receptors. J Neurosci Res 55(5):600–607
Nicholas AP, Hokfelt T, Pieribone VA (1996) The distribution and significance of CNS adrenoceptors examined with in situ hybridization. Trends Pharmacol Sci 17(7):245–255
Nishi A, Snyder GL, Greengard P (1997) Bidirectional regulation of DARPP-32 phosphorylation by dopamine. J Neurosci 17(21):8147–8155
Nishi A, Watanabe Y, Higashi H, Tanaka M, Nairn AC, Greengard P (2005) Glutamate regulation of DARPP-32 phosphorylation in neostriatal neurons involves activation of multiple signaling cascades. Proc Natl Acad Sci USA 102(4):1199–1204
Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322
Nowak P, Bortel A, Dabrowska J, Biedka I, Slomian G, Roczniak W, Kostrzewa RM, Brus R (2008) Histamine H(3) receptor ligands modulate L-dopa-evoked behavioral responses and l-dopa derived extracellular dopamine in dopamine-denervated rat striatum. Neurotox Res 13:231–240
Nutt JG (1990) Levodopa-induced dyskinesia: review, observations, and speculations. Neurology 40(2):340–345
Nutt JG (2008) Pharmacokinetics and pharmacodynamics of levodopa. Mov Disord 23(Suppl 3):S580–S584
Nutt JG, Gunzler SA, Kirchhoff T, Hogarth P, Weaver JL, Krams M, Jamerson B, Menniti FS, Landen JW (2008) Effects of a NR2B selective NMDA glutamate antagonist, CP-101, 606, on dyskinesia and Parkinsonism. Mov Disord 23(13):1860–1866
Obeso JA, Olanow CW, Nutt JG (2000a) Levodopa motor complications in Parkinson’s disease. Trends Neurosci 23(10 Suppl):S2–S7
Obeso JA, Rodriguez-Oroz MC, Rodriguez M, DeLong, Olanow CW (2000b) Pathophysiology of levodopa-induced dyskinesias in Parkinson’s disease: problems with the current model. Ann Neurol 47(4 Suppl 1):S22–S32 discussion S32–24
Obeso JA, Marin C, Rodriguez-Oroz C, Blesa J, Benitez-Temino B, Mena-Segovia J, Rodriguez M, Olanow CW (2008) The basal ganglia in Parkinson’s disease: current concepts and unexplained observations. Ann Neurol 64(Suppl 2):S30–S46
Oh JD, Russell DS, Vaughan CL, Chase TN (1998) Enhanced tyrosine phosphorylation of striatal NMDA receptor subunits: effect of dopaminergic denervation and l-DOPA administration. Brain Res 813(1):150–159
Oh JD, Vaughan CL, Chase TN (1999) Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal NMDA receptor subunits. Brain Res 821(2):433–442
Oh JD, Bibbiani F, Chase TN (2002) Quetiapine attenuates levodopa-induced motor complications in rodent and primate parkinsonian models. Exp Neurol 177(2):557–564
Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, Freeman TB (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54(3):403–414
Olanow CW, Damier P, Goetz CG, Mueller T, Nutt J, Rascol O, Serbanescu A, Deckers F, Russ H (2004) Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). Clin Neuropharmacol 27(2):58–62
Onn SP, West AR, Grace AA (2000) Dopamine-mediated regulation of striatal neuronal and network interactions. Trends Neurosci 23(10 Suppl):S48–S56
Onofrj M, Bonanni L, Thomas A (2008) An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs 17:1115–1125
Ossowska K, Konieczny J, Wolfarth S, Wieronska J, Pilc A (2001) Blockade of the metabotropic glutamate receptor subtype 5 (mGluR5) produces antiparkinsonian-like effects in rats. Neuropharmacology 41(4):413–420
Ossowska K, Konieczny J, Wolfarth S, Pilc A (2005) MTEP, a new selective antagonist of the metabotropic glutamate receptor subtype 5 (mGluR5), produces antiparkinsonian-like effects in rats. Neuropharmacology 49(4):447–455
Ouattara B, Belkhir S, Morissette M, Dridi M, Samadi P, Gregoire L, Meltzer LT, Di Paolo T (2009a) Implication of NMDA receptors in the antidyskinetic activity of cabergoline, CI-1041, and Ro 61–8048 in MPTP monkeys with levodopa-induced dyskinesias. J Mol Neurosci 38(2):128–142
Ouattara B, Gregoire L, Morissette M, Gasparini F, Vranesic I, Bilbe G, Johns DR, Rajput A, Hornykiewicz O, Rajput AH, Gomez-Mancilla B, Di Paolo T (2009b) Metabotropic glutamate receptor type 5 in levodopa-induced motor complications. Neurobiol Aging
Padovan-Neto FE, Echeverry MB, Tumas V, Del-Bel EA (2009) Nitric oxide synthase inhibition attenuates l-DOPA-induced dyskinesias in a rodent model of Parkinson’s disease. Neuroscience 159(3):927–935
Paladini CA, Williams JT (2004) Noradrenergic inhibition of midbrain dopamine neurons. J Neurosci 24(19):4568–4575
Paladini CA, Fiorillo CD, Morikawa H, Williams JT (2001) Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons. Nat Neurosci 4(3):275–281
Park DJ, West AR (2009) Regulation of striatal nitric oxide synthesis by local dopamine and glutamate interactions. J Neurochem 111(6):1457–1465
Parkin SG, Gregory RP, Scott R, Bain P, Silburn P, Hall B, Boyle R, Joint C, Aziz TZ (2002) Unilateral and bilateral pallidotomy for idiopathic Parkinson’s disease: a case series of 115 patients. Mov Disord 17(4):682–692
Pavon N, Martin AB, Mendialdua A, Moratalla R (2006) ERK phosphorylation and FosB expression are associated with l-DOPA-induced dyskinesia in hemiparkinsonian mice. Biol Psychiatry 59(1):64–74
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 10:731–740
Pearce RK, Jackson M, Britton DR, Shiosaki K, Jenner P, Marsden CD (1999) Actions of the D1 agonists A-77636 and A-86929 on locomotion and dyskinesia in MPTP-treated l-dopa-primed common marmosets. Psychopharmacology (Berl) 142(1):51–60
Pearce RK, Heikkila M, Linden IB, Jenner P (2001) l-dopa induces dyskinesia in normal monkeys: behavioural and pharmacokinetic observations. Psychopharmacology (Berl) 156(4):402–409
Peckys D, Landwehrmeyer GB (1999) Expression of mu, kappa, and delta opioid receptor messenger RNA in the human CNS: a 33P in situ hybridization study. Neuroscience 88(4):1093–1135
Pertwee RG (2006) Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147(Suppl 1):S163–S171
Picconi B, Centonze D, Hakansson K, Bernardi G, Greengard P, Fisone G, Cenci MA, Calabresi P (2003) Loss of bidirectional striatal synaptic plasticity in l-DOPA-induced dyskinesia. Nat Neurosci 6(5):501–506
Piggott MA, Marshall EF, Thomas N, Lloyd S, Court JA, Jaros E, Costa D, Perry RH, Perry EK (1999) Dopaminergic activities in the human striatum: rostrocaudal gradients of uptake sites and of D1 and D2 but not of D3 receptor binding or dopamine. Neuroscience 90(2):433–445
Pinna A (2009) Novel investigational adenosine A2A receptor antagonists for Parkinson’s disease. Expert Opin Investig Drugs 18(11):1619–1631
Pinna A, Fenu S, Morelli M (2001) Motor stimulant effects of the adenosine A2A receptor antagonist SCH 58261 do not develop tolerance after repeated treatments in 6-hydroxydopamine-lesioned rats. Synapse 39(3):233–238
Piomelli D (2003) The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 4(11):873–884
Pisani A, Fezza F, Galati S, Battista N, Napolitano S, Finazzi-Agro A, Bernardi G, Brusa L, Pierantozzi M, Stanzione P, Maccarrone M (2005) High endogenous cannabinoid levels in the cerebrospinal fluid of untreated Parkinson’s disease patients. Ann Neurol 57(5):777–779
Politis M, Wu K, Loane C, Quinn NP, Brooks DJ, Rehncrona S, Bjorklund A, Lindvall O, Piccini P (2010) Serotonergic neurons mediate dyskinesia side effects in Parkinson’s patients with neural transplants. Sci Transl Med 2(38):38ra46
Ponce FA, Lozano AM (2010) Deep brain stimulation state of the art and novel stimulation targets. Prog Brain Res 184:311–324
Porter RH, Greene JG, Higgins DS Jr, Greenamyre JT (1994) Polysynaptic regulation of glutamate receptors and mitochondrial enzyme activities in the basal ganglia of rats with unilateral dopamine depletion. J Neurosci 14(11 Pt 2):7192–7199
Prast H, Tran MH, Fischer H, Kraus M, Lamberti C, Grass K, Philippu A (1999a) Histaminergic neurons modulate acetylcholine release in the ventral striatum: role of H3 histamine receptors. Naunyn Schmiedebergs Arch Pharmacol 360:558–564
Prast H, Tran MH, Lamberti C, Fischer H, Kraus M, Grass K, Philippu A (1999b) Histaminergic neurons modulate acetylcholine release in the ventral striatum: role of H1 and H2 histamine receptors. Naunyn Schmiedebergs Arch Pharmacol 360:552–557
Rascol O (2000) Medical treatment of levodopa-induced dyskinesias. Ann Neurol 47(4 Suppl 1):S179–S188
Rascol O (2011) Drugs and drug delivery in PD: optimizing control of symptoms with pramipexole prolonged-release. Eur J Neurol 18(Suppl 1):3–10
Rascol O, Fabre N, Blin O, Poulik J, Sabatini U, Senard JM, Ane M, Montastruc JL, Rascol A (1994) Naltrexone, an opiate antagonist, fails to modify motor symptoms in patients with Parkinson’s disease. Mov Disord 9(4):437–440
Rascol O, Blin O, Thalamas C, Descombes S, Soubrouillard C, Azulay P, Fabre N, Viallet F, Lafnitzegger K, Wright S, Carter JH, Nutt JG (1999) ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson’s disease. Ann Neurol 45:736–741
Rascol O, Arnulf I, Peyro-Saint Paul H, Brefel-Courbon C, Vidailhet M, Thalamas C, Bonnet AM, Descombes S, Bejjani B, Fabre N, Montastruc JL, Agid Y (2001a) Idazoxan, an alpha-2 antagonist, and l-DOPA-induced dyskinesias in patients with Parkinson’s disease. Mov Disord 16(4):708–713
Rascol O, Nutt JG, Blin O, Goetz CG, Trugman JM, Soubrouillard C, Carter JH, Currie LJ, Fabre N, Thalamas C, Giardina WW, Wright S (2001b) Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease. Arch Neurol 58(2):249–254
Richardson PJ, Kase H, Jenner PG (1997) Adenosine A2A receptor antagonists as new agents for the treatment of Parkinson’s disease. Trends Pharmacol Sci 18(9):338–344
Rinne JO, Anichtchik OV, Eriksson KS, Kaslin J, Tuomisto L, Kalimo H, Roytta M, Panula P (2002) Increased brain histamine levels in Parkinson’s disease but not in multiple system atrophy. J Neurochem 81:954–960
Rodrigues RJ, Alfaro TM, Rebola N, Oliveira CR, Cunha RA (2005) Co-localization and functional interaction between adenosine A(2A) and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J Neurochem 92(3):433–441
Rodriguez M, Gonzalez-Hernandez T (1999) Electrophysiological and morphological evidence for a GABAergic nigrostriatal pathway. J Neurosci 19(11):4682–4694
Rommelfanger KS, Weinshenker D (2007) Norepinephrine: the redheaded stepchild of Parkinson’s disease. Biochem Pharmacol 74(2):177–190
Rosin DL, Hettinger BD, Lee A, Linden J (2003) Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function. Neurology 61(11 Suppl 6):S12–S18
Rouse ST, Marino MJ, Bradley SR, Awad H, Wittmann M, Conn PJ (2000) Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinson’s disease and related disorders. Pharmacol Ther 88(3):427–435
Rozas G, Liste I, Guerra MJ, Labandeira-Garcia JL (1998) Sprouting of the serotonergic afferents into striatum after selective lesion of the dopaminergic system by MPTP in adult mice. Neurosci Lett 245(3):151–154
Rylander D, Recchia A, Mela F, Dekundy A, Danysz W, Cenci MA (2009) Pharmacological modulation of glutamate transmission in a rat model of l-DOPA-induced dyskinesia: effects on motor behavior and striatal nuclear signaling. J Pharmacol Exp Ther 330(1):227–235
Rylander D, Iderberg H, Li Q, Dekundy A, Zhang J, Li H, Baishen R, Danysz W, Bezard E, Cenci MA (2010a) A mGluR5 antagonist under clinical development improves l-DOPA-induced dyskinesia in parkinsonian rats and monkeys. Neurobiol Dis 39(3):352–361
Rylander D, Parent M, O’Sullivan SS, Dovero S, Lees AJ, Bezard E, Descarries L, Cenci MA (2010b) Maladaptive plasticity of serotonin axon terminals in levodopa-induced dyskinesia. Ann Neurol 68(5):619–628
Ryu JH, Yanai K, Watanabe T (1994) Marked increase in histamine H3 receptors in the striatum and substantia nigra after 6-hydroxydopamine-induced denervation of dopaminergic neurons: an autoradiographic study. Neurosci Lett 178:19–22
Ryu JH, Yanai K, Sakurai E, Kim CY, Watanabe T (1995) Ontogenetic development of histamine receptor subtypes in rat brain demonstrated by quantitative autoradiography. Brain Res Dev Brain Res 87:101–110
Sallinen J, Haapalinna A, Viitamaa T, Kobilka BK, Scheinin M (1998a) d-amphetamine and l-5-hydroxytryptophan-induced behaviours in mice with genetically-altered expression of the alpha2C-adrenergic receptor subtype. Neuroscience 86(3):959–965
Sallinen J, Haapalinna A, Viitamaa T, Kobilka BK, Scheinin M (1998b) Adrenergic alpha2C-receptors modulate the acoustic startle reflex, prepulse inhibition, and aggression in mice. J Neurosci 18(8):3035–3042
Samadi P, Gregoire L, Bedard PJ (2004) The opioid agonist morphine decreases the dyskinetic response to dopaminergic agents in parkinsonian monkeys. Neurobiol Dis 16:246–253
Samadi P, Gregoire L, Hadj Tahar A, Di Paolo T, Rouillard C, Bedard PJ (2005) Naltrexone in the short-term decreases antiparkinsonian response to l-Dopa and in the long-term increases dyskinesias in drug-naive parkinsonian monkeys. Neuropharmacology 49:165–173
Samadi P, Bedard PJ, Rouillard C (2006) Opioids and motor complications in Parkinson’s disease. Trends Pharmacol Sci 27(10):512–517
Samadi P, Gregoire L, Morissette M, Calon F, Hadj Tahar A, Dridi M, Belanger N, Meltzer LT, Bedard PJ, Di Paolo T (2008) mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys. Neurobiol Aging 29(7):1040–1051
Sammut S, Dec A, Mitchell D, Linardakis J, Ortiguela M, West AR (2006) Phasic dopaminergic transmission increases NO efflux in the rat dorsal striatum via a neuronal NOS and a dopamine D(1/5) receptor-dependent mechanism. Neuropsychopharmacology 31(3):493–505
Sammut S, Bray KE, West AR (2007) Dopamine D2 receptor-dependent modulation of striatal NO synthase activity. Psychopharmacology (Berl) 191(3):793–803
Sancesario G, Morello M, Reiner A, Giacomini P, Massa R, Schoen S, Bernardi G (2000) Nitrergic neurons make synapses on dual-input dendritic spines of neurons in the cerebral cortex and the striatum of the rat: implication for a postsynaptic action of nitric oxide. Neuroscience 99(4):627–642
Sandyk R, Snider SR (1986) Naloxone treatment of l-dopa-induced dyskinesias in Parkinson’s disease. Am J Psychiatry 143(1):118
Santiago M, Matarredona ER, Machado A, Cano J (1998) Influence of serotoninergic drugs on in vivo dopamine extracellular output in rat striatum. J Neurosci Res 52(5):591–598
Santini E, Valjent E, Usiello A, Carta M, Borgkvist A, Girault JA, Herve D, Greengard P, Fisone G (2007) Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in l-DOPA-induced dyskinesia. J Neurosci 27(26):6995–7005
Santini E, Alcacer C, Cacciatore S, Heiman M, Herve D, Greengard P, Girault JA, Valjent E, Fisone G (2009) l-DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice. J Neurochem 108(3):621–633
Santini E, Sgambato-Faure V, Li Q, Savasta M, Dovero S, Fisone G, Bezard E (2010) Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in l-DOPA-induced dyskinesia. PLoS One 5:e12322
Savola JM, Hill M, Engstrom M, Merivuori H, Wurster S, McGuire SG, Fox SH, Crossman AR, Brotchie JM (2003) Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson’s disease. Mov Disord 18(8):872–883
Schapira AH (2010) Safinamide in the treatment of Parkinson’s disease. Expert Opin Pharmacother 11:2261–2268
Schiffmann SN, Vanderhaeghen JJ (1993) Age-related loss of mRNA encoding adenosine A2 receptor in the rat striatum. Neurosci Lett 158(2):121–124
Schiffmann SN, Jacobs O, Vanderhaeghen JJ (1991) Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem 57(3):1062–1067
Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferre S (2007) Adenosine A2A receptors and basal ganglia physiology. Prog Neurobiol 83(5):277–292
Schlicker E, Kathmann M (2001) Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 22(11):565–572
Schlicker E, Fink K, Detzner M, Gothert M (1993) Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors. J Neural Transm Gen Sect 93:1–10
Schrag A, Schott JM (2006) Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol 5(4):355–363
Schrag A, Ben-Shlomo Y, Brown R, Marsden CD, Quinn N (1998) Young-onset Parkinson’s disease revisited—clinical features, natural history, and mortality. Mov Disord 13(6):885–894
Seeman P, Guttman M (1987) Dopamine receptor elevation in denervated tissues. Ann Neurol 21:412–415
Segovia G, Mora F, Crossman AR, Brotchie JM (2003) Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high-dose levodopa in the reserpine-treated rat model of Parkinson’s disease. Mov Disord 18(2):138–149
Sershen H, Hashim A, Lajtha A (2000) Serotonin-mediated striatal dopamine release involves the dopamine uptake site and the serotonin receptor. Brain Res Bull 53(3):353–357
Shiosaki K, Jenner P, Asin KE, Britton DR, Lin CW, Michaelides M, Smith L, Bianchi B, Didomenico S, Hodges L, Hong Y, Mahan L, Mikusa J, Miller T, Nikkel A, Stashko M, Witte D, Williams M (1996) ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson’s disease. J Pharmacol Exp Ther 276(1):150–160
Silverdale MA, Crossman AR, Brotchie JM (2002) Striatal AMPA receptor binding is unaltered in the MPTP-lesioned macaque model of Parkinson’s disease and dyskinesia. Exp Neurol 174(1):21–28
Smith AD, Bolam JP (1990) The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones. Trends Neurosci 13:259–265
Smith LA, Tel BC, Jackson MJ, Hansard MJ, Braceras R, Bonhomme C, Chezaubernard C, Del Signore S, Rose S, Jenner P (2002) Repeated administration of piribedil induces less dyskinesia than l-dopa in MPTP-treated common marmosets: a behavioural and biochemical investigation. Mov Disord 17:887–901
Smith LA, Jackson MJ, Johnston L, Kuoppamaki M, Rose S, Al-Barghouthy G, Del Signore S, Jenner P (2006) Switching from levodopa to the long-acting dopamine D2/D3 agonist piribedil reduces the expression of dyskinesia while maintaining effective motor activity in MPTP-treated primates. Clin Neuropharmacol 29(3):112–125
Sossi V, de la Fuente-Fernandez R, Schulzer M, Adams J, Stoessl J (2006) Age-related differences in levodopa dynamics in Parkinson’s: implications for motor complications. Brain 129(Pt 4):1050–1058
Stocchi F (2009) The therapeutic concept of continuous dopaminergic stimulation (CDS) in the treatment of Parkinson’s disease. Parkinsonism Relat Disord 15(Suppl 3):S68–S71
Stocchi F, Vacca L, Grassini P, De Pandis MF, Battaglia G, Cattaneo C, Fariello RG (2006) Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition. Neurology 67:S24–S29
Stocchi F, Tagliati M, Olanow CW (2008) Treatment of levodopa-induced motor complications. Mov Disord 23(Suppl 3):S599–S612
Stockwell KA, Scheller D, Rose S, Jackson MJ, Tayarani-Binazir K, Iravani MM, Smith LA, Olanow CW, Jenner P (2009) Continuous administration of rotigotine to MPTP-treated common marmosets enhances anti-parkinsonian activity and reduces dyskinesia induction. Exp Neurol 219:533–542
Stockwell KA, Scheller DK, Smith LA, Rose S, Iravani MM, Jackson MJ, Jenner P (2010) Continuous rotigotine administration reduces dyskinesia resulting from pulsatile treatment with rotigotine or l-DOPA in MPTP-treated common marmosets. Exp Neurol 221(1):79–85
Stoof JC, Kebabian JW (1981) Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 294(5839):366–368
Suen PC, Wu K, Xu JL, Lin SY, Levine ES, Black IB (1998) NMDA receptor subunits in the postsynaptic density of rat brain: expression and phosphorylation by endogenous protein kinases. Brain Res Mol Brain Res 59(2):215–228
Surmeier DJ, Ding J, Day M, Wang Z, Shen W (2007) D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 30(5):228–235
Suzuki T, Takamori K, Misawa M, Onodera K (1995) Effects of the histaminergic system on the morphine-induced conditioned place preference in mice. Brain Res 675:195–202
Svenningsson P, Le Moine C, Aubert I, Burbaud P, Fredholm BB, Bloch B (1998) Cellular distribution of adenosine A2A receptor mRNA in the primate striatum. J Comp Neurol 399(2):229–240
Swanson LW, Hartman BK (1975) The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-beta-hydroxylase as a marker. J Comp Neurol 163(4):467–505
Takagi H, Morishima Y, Matsuyama T, Hayashi H, Watanabe T, Wada H (1986) Histaminergic axons in the neostriatum and cerebral cortex of the rat: a correlated light and electron microscopic immunocytochemical study using histidine decarboxylase as a marker. Brain Res 364:114–123
Takeda N, Inagaki S, Shiosaka S, Taguchi Y, Oertel WH, Tohyama M, Watanabe T, Wada H (1984) Immunohistochemical evidence for the coexistence of histidine decarboxylase-like and glutamate decarboxylase-like immunoreactivities in nerve cells of the magnocellular nucleus of the posterior hypothalamus of rats. Proc Natl Acad Sci USA 81:7647–7650
Tani Y, Ogata A, Koyama M, Inoue T (2010) Effects of piclozotan (SUN N4057), a partial serotonin 1A receptor agonist, on motor complications induced by repeated administration of levodopa in parkinsonian rats. Eur J Pharmacol 649:218–223
Taylor JL, Bishop C, Ullrich T, Rice KC, Walker PD (2006) Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated rotational behavior but not l-DOPA-induced abnormal involuntary movements in the unilateral dopamine-depleted rat. Neuropharmacology 50(6):761–768
Tel BC, Zeng BY, Cannizzaro C, Pearce RK, Rose S, Jenner P (2002) Alterations in striatal neuropeptide mRNA produced by repeated administration of l-DOPA, ropinirole or bromocriptine correlate with dyskinesia induction in MPTP-treated common marmosets. Neuroscience 115(4):1047–1058
Tingley WG, Ehlers MD, Kameyama K, Doherty C, Ptak JB, Riley CT, Huganir RL (1997) Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-d-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies. J Biol Chem 272(8):5157–5166
Togasaki DM, Tan L, Protell P, Di Monte DA, Quik M, Langston JW (2001) Levodopa induces dyskinesias in normal squirrel monkeys. Ann Neurol 50(2):254–257
Togasaki DM, Protell P, Tan LC, Langston JW, Di Monte DA, Quik M (2005) Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa. Neuropharmacology 48(3):398–405
Tousi B, Subramanian T (2005) The effect of levetiracetam on levodopa induced dyskinesia in patients with Parkinson’s disease. Parkinsonism Relat Disord 11:333–334
Trabace L, Kendrick KM (2000) Nitric oxide can differentially modulate striatal neurotransmitter concentrations via soluble guanylate cyclase and peroxynitrite formation. J Neurochem 75(4):1664–1674
Trabucchi M, Bassi S, Frattola L (1982) Effect of naloxone on the “on–off” syndrome in patients receiving long-term levodopa therapy. Arch Neurol 39(2):120–121
Ulusoy A, Sahin G, Kirik D (2010) Presynaptic dopaminergic compartment determines the susceptibility to l-DOPA-induced dyskinesia in rats. Proc Natl Acad Sci USA 107(29):13159–13164
van der Stelt M, Fox SH, Hill M, Crossman AR, Petrosino S, Di Marzo V, Brotchie JM (2005) 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 19(9):1140–1142
Verhagen Metman L, Del Dotto P, van den Munckhof P, Fang J, Mouradian MM, Chase TN (1998) Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology 50(5):1323–1326
Vincent SR, Kimura H (1992) Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience 46(4):755–784
Vizuete ML, Traiffort E, Bouthenet ML, Ruat M, Souil E, Tardivel-Lacombe J, Schwartz JC (1997) Detailed mapping of the histamine H2 receptor and its gene transcripts in guinea-pig brain. Neuroscience 80:321–343
Vogt BA, Hof PR, Friedman DP, Sikes RW, Vogt LJ (2008) Norepinephrinergic afferents and cytology of the macaque monkey midline, mediodorsal, and intralaminar thalamic nuclei. Brain Struct Funct 212(6):465–479
Voon V, Fernagut PO, Wickens J, Baunez C, Rodriguez M, Pavon N, Juncos JL, Obeso JA, Bezard E (2009) Chronic dopaminergic stimulation in Parkinson’s disease: from dyskinesias to impulse control disorders. Lancet Neurol 8(12):1140–1149
Wada H, Inagaki N, Yamatodani A, Watanabe T (1991) Is the histaminergic neuron system a regulatory center for whole-brain activity? Trends Neurosci 14:415–418
Walsh S, Mnich K, Mackie K, Gorman AM, Finn DP, Dowd E (2010) Loss of cannabinoid CB1 receptor expression in the 6-hydroxydopamine-induced nigrostriatal terminal lesion model of Parkinson’s disease in the rat. Brain Res Bull 81(6):543–548
Wang YT, Salter MW (1994) Regulation of NMDA receptors by tyrosine kinases and phosphatases. Nature 369(6477):233–235
Wang H, Gracy KN, Pickel VM (1999) Mu-opioid and NMDA-type glutamate receptors are often colocalized in spiny neurons within patches of the caudate-putamen nucleus. J Comp Neurol 412(1):132–146
Watanabe T, Taguchi Y, Shiosaka S, Tanaka J, Kubota H, Terano Y, Tohyama M, Wada H (1984) Distribution of the histaminergic neuron system in the central nervous system of rats; a fluorescent immunohistochemical analysis with histidine decarboxylase as a marker. Brain Res 295:13–25
Westin JE, Vercammen L, Strome EM, Konradi C, Cenci MA (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(7):800–810
Wichmann T, DeLong MR (2006) Basal ganglia discharge abnormalities in Parkinson’s disease. J Neural Transm Suppl 70:21–25
Williams JT, Christie MJ, Manzoni O (2001) Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev 81(1):299–343
Wilson RI, Nicoll RA (2002) Endocannabinoid signaling in the brain. Science 296(5568):678–682
Wolf E, Seppi K, Katzenschlager R, Hochschorner G, Ransmayr G, Schwingenschuh P, Ott E, Kloiber I, Haubenberger D, Auff E, Poewe W (2010) Long-term antidyskinetic efficacy of amantadine in Parkinson’s disease. Mov Disord 25(10):1357–1363
Wolz M, Lohle M, Strecker K, Schwanebeck U, Schneider C, Reichmann H, Grahlert X, Schwarz J, Storch A (2010) Levetiracetam for levodopa-induced dyskinesia in Parkinson’s disease: a randomized, double-blind, placebo-controlled trial. J Neural Transm 117:1279–1286
Wong PT, Feng H, Teo WL (1995) Interaction of the dopaminergic and serotonergic systems in the rat striatum: effects of selective antagonists and uptake inhibitors. Neurosci Res 23(1):115–119
Xiao D, Bastia E, Xu YH, Benn CL, Cha JH, Peterson TS, Chen JF, Schwarzschild MA (2006) Forebrain adenosine A2A receptors contribute to l-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice. J Neurosci 26(52):13548–13555
Yanovsky Y, Li S, Klyuch BP, Yao Q, Blandina P, Passani MB, Lin JS, Haas HL, Sergeeva OA (2011) l-Dopa activates histaminergic neurons. J Physiol 589:1349–1366
Yu XM, Askalan R, Keil GJ 2nd, Salter MW (1997) NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275(5300):674–678
Zavitsanou K, Mitsacos A, Giompres P, Kouvelas ED (1996) Changes in [3H]AMPA and [3H]kainate binding in rat caudate-putamen and nucleus accumbens after 6-hydroxydopamine lesions of the medial forebrain bundle: an autoradiographic study. Brain Res 731(1–2):132–140
Zeng BY, Dass B, Owen A, Rose S, Cannizzaro C, Tel BC, Jenner P (1999) Chronic l-DOPA treatment increases striatal cannabinoid CB1 receptor mRNA expression in 6-hydroxydopamine-lesioned rats. Neurosci Lett 276(2):71–74
Zeng BY, Pearce RK, MacKenzie GM, Jenner P (2000) Alterations in preproenkephalin and adenosine-2a receptor mRNA, but not preprotachykinin mRNA correlate with occurrence of dyskinesia in normal monkeys chronically treated with l-DOPA. Eur J Neurosci 12(3):1096–1104
Zeng BY, Iravani MM, Jackson MJ, Rose S, Parent A, Jenner P (2010) Morphological changes in serotoninergic neurites in the striatum and globus pallidus in levodopa primed MPTP treated common marmosets with dyskinesia. Neurobiol Dis 40(3):599–607
Zesiewicz TA, Sullivan KL, Maldonado JL, Tatum WO, Hauser RA (2005) Open-label pilot study of levetiracetam (Keppra) for the treatment of levodopa-induced dyskinesias in Parkinson’s disease. Mov Disord 20:1205–1209
Zhang W, Klimek V, Farley JT, Zhu MY, Ordway GA (1999) Alpha2C adrenoceptors inhibit adenylyl cyclase in mouse striatum: potential activation by dopamine. J Pharmacol Exp Ther 289(3):1286–1292
Zhang X, Andren PE, Svenningsson P (2007) Changes on 5-HT2 receptor mRNAs in striatum and subthalamic nucleus in Parkinson’s disease model. Physiol Behav 92(1–2):29–33
Zhou FC, Bledsoe S, Murphy J (1991) Serotonergic sprouting is induced by dopamine-lesion in substantia nigra of adult rat brain. Brain Res 556(1):108–116
Zhuang X, Belluscio L, Hen R (2000) G(olf)alpha mediates dopamine D1 receptor signaling. J Neurosci 20(16):RC91
Zimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI (1999) Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 96(10):5780–5785
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Iravani, M.M., Jenner, P. Mechanisms underlying the onset and expression of levodopa-induced dyskinesia and their pharmacological manipulation. J Neural Transm 118, 1661–1690 (2011). https://doi.org/10.1007/s00702-011-0698-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-011-0698-2