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Journal of Neural Transmission

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02.02.2018 | Neurology and Preclinical Neurological Studies - Review Article

Role of adenosine A_2A receptors in motor control: relevance to Parkinson’s disease and dyskinesia

verfasst von: Annalisa Pinna, Marcello Serra, Micaela Morelli, Nicola Simola

Erschienen in: Journal of Neural Transmission | Ausgabe 8/2018

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Abstract

Adenosine is an endogenous purine nucleoside that regulates several physiological functions, at the central and peripheral levels. Besides, adenosine has emerged as a major player in the regulation of motor behavior. In fact, adenosine receptors of the A_2A subtype are highly enriched in the caudate–putamen, which is richly innervated by dopamine. Moreover, several studies in experimental animals have consistently demonstrated that the pharmacological antagonism of A_2A receptors has a facilitatory influence on motor behavior. Taken together, these findings have envisaged A_2A receptors as a promising target for symptomatic therapies aimed at ameliorating motor deficits. Accordingly, A_2A receptor antagonists have been extensively studied as new agents for the treatment of Parkinson’s disease (PD), the epitome of motor disorders. In this review, we provide an overview of the effects that adenosine A_2A receptor antagonists elicit in rodent and primate experimental models of PD, with regard to the counteraction of motor deficits as well as to manifestation of dyskinesia and motor fluctuations. Moreover, we briefly present the results of clinical trials of A_2A receptor antagonists in PD patients experiencing motor fluctuations, with particular regard to dyskinesia. Finally, we discuss the interaction between A_2A receptor antagonists and serotonin receptor agonists, since combined administration of these drugs has recently emerged as a new potential therapeutic strategy in the treatment of dyskinesia.

Antonelli T, Fuxe K, Tomasini MC et al (2005) Effects of sarizotan on the corticostriatal glutamate pathways. Synapse 58:193–199. https://doi.org/10.1002/syn.20195 PubMedCrossRef

Aoyama S, Kase H, Borrelli E (2000) Rescue of locomotor impairment in dopamine D₂ receptor-deficient mice by an adenosine A_2A receptor antagonist. J Neurosci 20:5848–5852PubMedCrossRef

Armentero MT, Pinna A, Ferré S et al (2011) Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson’s disease. Pharmacol Ther 132:280–299. https://doi.org/10.1016/j.pharmthera.2011.07.004 PubMedPubMedCentralCrossRef

Augood SJ, Emson PC (1994) Adenosine A_2a receptor mRNA is expressed by enkephalin cells but not somatostatin cells in rat striatum: a co-expression study. Mol Brain Res 22:204–210. https://doi.org/10.1016/0169-328X(94)90048-5 PubMedCrossRef

Bara-Jimenez W, Sherzai A, Dimitrova T et al (2003) Adenosine A_2A receptor antagonist treatment of Parkinson’s disease. Neurology 61:293–296. https://doi.org/10.1212/01.WNL.0000073136.00548.D4 PubMedCrossRef

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. https://doi.org/10.1016/j.pneurobio.2015.07.002 PubMedCrossRef

Baumgarten HG, Grozdanovic Z (1995) Psychopharmacology of central serotonergic systems. Pharmacopsychiatry 2:73–79. https://doi.org/10.1055/s-2007-979623 CrossRef

Bezard E, Carta M (2015) Could the serotonin theory give rise to a treatment for levodopa-induced dyskinesia in Parkinson’s disease? Brain 138:829–830. https://doi.org/10.1093/brain/awu407 PubMedCrossRef

Bezard E, Muñoz A, Tronci E et al (2013a) Anti-dyskinetic effect of anpirtoline in animal models of l-DOPA-induced dyskinesia. Neurosci Res 77:242–246. https://doi.org/10.1016/j.neures.2013.10.002 PubMedCrossRef

Bezard E, Tronci E, Pioli EY et al (2013b) Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia. Mov Disord 28:1088–1096. https://doi.org/10.1002/mds.25366 PubMedCrossRef

Bibbiani F, Oh JD, Petzer JP et al (2003) A_2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease. Exp Neurol 184:285–294. https://doi.org/10.1016/S0014-4886(03)00250-4 PubMedCrossRef

Bibbiani F, Costantini LC, Patel R, Chase TN (2005) Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates. Exp Neurol 192:73–78. https://doi.org/10.1016/j.expneurol.2004.11.013 PubMedCrossRef

Bogenpohl JW, Ritter SL, Hall RA, Smith Y (2012) Adenosine A_2A receptor in the monkey basal ganglia: ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum. J Comp Neurol 520:570–589. https://doi.org/10.1002/cne.22751 PubMedPubMedCentralCrossRef

Boison D, Chen JF, Fredholm BB (2010) Adenosine signalling and function in glial cells. Cell Death Differ 17:1071–1082. https://doi.org/10.1038/cdd.2009.131 PubMedCrossRef

Bové J, Marin C, Bonastre M, Tolosa E (2002) Adenosine A_2A antagonism reverses levodopa-induced motor alterations in hemiparkinsonian rats. Synapse 46:251–257. https://doi.org/10.1002/syn.10112 PubMedCrossRef

Bové J, Serrats J, Mengod G et al (2006) Reversion of levodopa-induced motor fluctuations by the A_2A antagonist CSC is associated with an increase in striatal preprodynorphin mRNA expression in 6-OHDA-lesioned rats. Synapse 59:435–444. https://doi.org/10.1002/syn.20259 PubMedCrossRef

Braak H, Del Tredici K, Rüb U et al (2013) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211. https://doi.org/10.1016/S0197-4580(02)00065-9 CrossRef

Burnstock G (2013) Introduction to purinergic signalling in the brain. Adv Exp Med Biol 986:1–12. https://doi.org/10.1007/978-94-007-4719-7_1 PubMedCrossRef

Burnstock G (2017) Purinergic signalling: therapeutic developments. Front Pharmacol 2017(8):661. https://doi.org/10.3389/fphar.2017.00661 CrossRef

Carriba P, Ortiz O, Patkar K et al (2007) Striatal adenosine A_2A and cannabinoid CB₁ receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology 32:2249–2259. https://doi.org/10.1038/sj.npp.1301375 PubMedCrossRef

Carriba P, Navarro G, Ciruela F et al (2008) Detection of heteromerization of more than two proteins by sequential BRET–FRET. Nat Methods 5:727–733. https://doi.org/10.1038/nmeth.1229 PubMedCrossRef

Carta M, Bezard E (2011) Contribution of pre-synaptic mechanisms to l-DOPA-induced dyskinesia. Neuroscience 198:245–251. https://doi.org/10.1016/j.neuroscience.2011.07.070 PubMedCrossRef

Carta M, Tronci E (2014) Serotonin system implication in l-DOPA-induced dyskinesia: from animal models to clinical investigations. Front Neurol 5:78. https://doi.org/10.3389/fneur.2014.00078 PubMedPubMedCentralCrossRef

Carta M, Carlsson T, Kirik D, Björklund A (2007) Dopamine released from 5-HT terminals is the cause of l-DOPA-induced dyskinesia in parkinsonian rats. Brain 130:1819–1833. https://doi.org/10.1093/brain/awm082 PubMedCrossRef

Cenci MA, Lundblad M (2006) Post-versus pre-synaptic plasticity in l-DOPA-induced dyskinesia. J Neurochem 99:381–392. https://doi.org/10.1111/j.1471-4159.2006.04124.x PubMedCrossRef

Cerri S, Siani F, Blandini F (2017) Investigational drugs in phase I and phase II for levodopa-induced dyskinesias. Expert Opin Investig Drugs 26:777–791. https://doi.org/10.1080/13543784.2017.1333598 PubMedCrossRef

Chen JF, Pedata F (2008) Modulation of ischemic brain injury and neuroinflammation by adenosine A_2A receptors. Curr Pharm Des 14:1490–1499. https://doi.org/10.2174/138161208784480126 PubMedCrossRef

Chen JF, Moratalla R, Impagnatiello F et al (2001) The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice. Proc Natl Acad Sci USA 98:1970–1975PubMedCrossRef

Ciruela F, Casadó V, Rodrigues RJ et al (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A₁–A_2A receptor heteromers. J Neurosci 26:2080–2087. https://doi.org/10.1523/JNEUROSCI.3574-05.2006 PubMedCrossRef

Collins-Praino LE, Paul NE, Rychalsky KL et al (2011) Pharmacological and physiological characterization of the tremulous jaw movement model of parkinsonian tremor: potential insights into the pathophysiology of tremor. Front Syst Neurosci 5:49. https://doi.org/10.3389/fnsys.2011.00049 PubMedPubMedCentralCrossRef

Cunha RA (2001) Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem Int 38:107–125. https://doi.org/10.1016/S0197-0186(00)00034-6 PubMedCrossRef

Delwaide PJ (2001) Parkinsonian rigidity. Funct Neurol 16:147–156PubMed

Dixon AK, Gubitz AK, Sirinathsinghji DJ et al (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:1461–1468. https://doi.org/10.1111/j.1476-5381.1996.tb15561.x PubMedPubMedCentralCrossRef

Dungo R, Deeks ED (2013) Istradefylline: first global approval. Drugs 73:875–882. https://doi.org/10.1007/s40265-013-0066-7 PubMedCrossRef

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. https://doi.org/10.1111/j.1476-5381.2011.01426.x PubMedPubMedCentralCrossRef

Factor SA, Wolski K, Togasaki DM et al (2013) Long-term safety and efficacy of preladenant in subjects with fluctuating Parkinson’s disease. Mov Disord 28:817–820. https://doi.org/10.1002/mds.25395 PubMedCrossRef

Feoktistov I, Biaggioni I (1997) Adenosine A₂B receptors. Pharmacol Rev 49:381–402PubMed

Ferré S, Fredholm BB, Morelli M et al (1997) Adenosine–dopamine receptor–receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 20:482–487. https://doi.org/10.1016/S0166-2236(97)01096-5 PubMedCrossRef

Ferré S, Karcz-Kubicha M, Hope BT et al (2002) Synergistic interaction between adenosine A_2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc Natl Acad Sci USA 99:11940–11945. https://doi.org/10.1073/pnas.172393799 PubMedCrossRef

Ferré S, Lluís C, Justinova Z et al (2010) Adenosine–cannabinoid receptor interactions. Implications for striatal function. Br J Pharmacol 160:443–453. https://doi.org/10.1111/j.1476-5381.2010.00723.x PubMedPubMedCentralCrossRef

Fredduzzi S, Moratalla R, Monopoli A et al (2002) Persistent behavioral sensitization to chronic l-DOPA requires A_2A adenosine receptors. J Neurosci 22:1054–1062PubMedCrossRef

Fredholm BB, Chen JF, Cunha RA et al (2005) Adenosine and brain function. Int Rev Neurobiol 63:191–270. https://doi.org/10.1016/S0074-7742(05)63007-3 PubMedCrossRef

Fredholm BB, IJzerman AP, Jacobson KA et al (2011) International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update. Pharmacol Rev 63:1–34. https://doi.org/10.1124/pr.110.003285 PubMedPubMedCentralCrossRef

Freitas ME, Fox SH (2016) Non dopaminergic treatments for Parkinson’s disease: current and future prospects. Neurodegener Dis Manag 6:249–268. https://doi.org/10.2217/nmt-2016-0005 PubMedPubMedCentralCrossRef

Fuxe K, Borroto-Escuela DO, Marcellino D et al (2012) GPCR heteromers and their allosteric receptor-receptorinteractions. Curr Med Chem 19:356–363. https://doi.org/10.2174/092986712803414259 PubMedCrossRef

Fuzzati-Armentero MT, Cerri S, Levandis G et al (2015) Dual target strategy: combining distinct non-dopaminergic treatments reduces neuronal cell loss and synergistically modulates l-DOPA-induced rotational behavior in a rodent model of Parkinson’s disease. J Neurochem 134:740–747. https://doi.org/10.1111/jnc.13162 PubMedCrossRef

Gebicke-Haerter PJ, Christoffel F, Timmer J et al (1996) Both adenosine A₁ and A₂-receptors are required to stimulate microglial proliferation. Neurochem Int 29:37–42. https://doi.org/10.1016/0197-0186(95)00137-9 PubMedCrossRef

Gerevich Z, Wirkner K, Illes P (2002) Adenosine A_2A receptors inhibit the N-methyl-d-aspartate component of excitatory synaptic currents in rat striatal neurons. Eur J Pharmacol 451:161–164. https://doi.org/10.1016/S0014-2999(02)02301-4 PubMedCrossRef

Gessi S, Merighi S, Varani K et al (2008) The A₃ adenosine receptor: an enigmatic player in cell biology. Pharmacol Ther 117:123–140. https://doi.org/10.1016/j.pharmthera.2007.09.002 PubMedCrossRef

Ghiglieri V, Mineo D, Vannelli A et al (2016) Modulation of serotonergic transmission by eltoprazine in l-DOPA-induced dyskinesia: behavioral, molecular and synapticmechanisms. Neurobiol Dis 86:140–153. https://doi.org/10.1016/j.nbd.2015.11.022 PubMedCrossRef

Goetz CG, Damier P, Hicking C et al (2007) Sarizotan as a treatment for dyskinesias in Parkinson’s disease: a double-blind placebo-controlled trial. Mov Disord 22:179–186. https://doi.org/10.1002/mds.21226 PubMedCrossRef

Grondin R, Bédard PJ, Tahar AH et al (1999) Antiparkinsonian effect of a new selective adenosine A_2A receptor antagonist in MPTP-treated monkeys. Neurology 52:1673–1677PubMedCrossRef

Hammarberg C, Schulte G, Fredholm BB (2003) Evidence for functional adenosine A₃ receptors in microglia cells. J Neurochem 86:1051–1054. https://doi.org/10.1046/j.1471-4159.2003.01919.x PubMedCrossRef

Hauser RA, Hubble JP, Truong DD, Istradefylline US-001 Study Group (2003) Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology 61:297–303PubMedCrossRef

Hauser RA, Cantillon M, Pourcher E et al (2011) Preladenant in patients with Parkinson’s disease and motor fluctuations: a phase 2, double-blind, randomised trial. Lancet Neurol 10:221–229. https://doi.org/10.1016/S1474-4422(11)70012-6 PubMedCrossRef

Hauser RA, Olanow CW, Kieburtz KD et al (2014) Tozadenant (SYN115) in patients with Parkinson’s disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol 13:767–776. https://doi.org/10.1016/S1474-4422(14)70148-6 PubMedCrossRef

Hauser RA, Stocchi F, Rascol O et al (2015) Preladenant as an adjunctive therapy with levodopa in Parkinson disease: two randomized clinical trials and lessons learned. JAMA Neurol 72:1491–1500. https://doi.org/10.1001/jamaneurol.2015.2268 PubMedCrossRef

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. https://doi.org/10.1006/exnr.1998.6819 PubMedCrossRef

Heumann R, Moratalla R, Herrero MT et al (2014) Dyskinesia in Parkinson’s disease: mechanisms and current non-pharmacological interventions. J Neurochem 130:472–489. https://doi.org/10.1111/jnc.12751 PubMedCrossRef

Hodgson RA, Bertorelli R, Varty GB et al (2009) Characterization of the potent and highly selective A_2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in rodent models of movement disorders and depression. J Pharmacol Exp Ther 330:294–303. https://doi.org/10.1124/jpet.108.149617 PubMedCrossRef

Hodgson RA, Bedard PJ, Varty GB et al (2010) Preladenant, a selective A(2A) receptor antagonist, is active in primate models of movement disorders. Exp Neurol 225:384–390. https://doi.org/10.1016/j.expneurol.2010.07.011 PubMedCrossRef

Hout P, Fox SH, Brotchie JM (2011) The serotonergic system in Parkinson’s disease. Prog Neurobiol 95:163–212. https://doi.org/10.1016/j.pneurobio.2011.08.004 CrossRef

Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72:165–229PubMedCrossRef

Jankovic J (2005) Motor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations. Mov Disord 11:S11–S16. https://doi.org/10.1002/mds.20458 CrossRef

Jenner P (2008) Molecular mechanisms of l-DOPA-induced dyskinesia. Nat Rev Neurosci 9:665–677. https://doi.org/10.1038/nrn2471 PubMedCrossRef

Jenner P (2014) An overview of adenosine A_2A receptor antagonists in Parkinson’s disease. Int Rev Neurobiol 119:71–86. https://doi.org/10.1016/B978-0-12-801022-8.00003-9 PubMedCrossRef

Jones CK, Bubser M, Thompson AD et al (2012) The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with l-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson’s disease. J Pharmacol Exp Ther 340:404–421. https://doi.org/10.1124/jpet.111.187443 PubMedPubMedCentralCrossRef

Jones N, Bleickardt C, Mullins D, Parker E, Hodgson R (2013) A_2A receptor antagonists do not induce dyskinesias in drug-naive or l-dopa sensitized rats. Brain Res Bull 98:163–169. https://doi.org/10.1016/j.brainresbull.2013.07.001 PubMedCrossRef

Kachroo A, Orlando LR, Grandy DK et al (2005) Interactions between metabotropic glutamate 5 and adenosine A_2A receptors in normal and parkinsonian mice. J Neurosci 25:10414–10419. https://doi.org/10.1523/JNEUROSCI.3660-05.2005 PubMedCrossRef

Kanda T, Uchida S (2014) Clinical/pharmacological aspect of adenosine A_2A receptor antagonist for dyskinesia. Int Rev Neurobiol 119:127–150. https://doi.org/10.1016/B978-0-12-801022-8.00006-4 PubMedCrossRef

Kanda T, Shiozaki S, Shimada J et al (1994) KF17837: a novel selective adenosine A_2A receptor antagonist with anticataleptic activity. Eur J Pharmacol 256:263–268. https://doi.org/10.1016/0014-2999(94)90551-7 PubMedCrossRef

Kanda T, Jackson MJ, Smith LA et al (1998) Adenosine A_2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 43:507–513. https://doi.org/10.1002/ana.410430415 PubMedCrossRef

Kanda T, Jackson MJ, Smith LA et al (2000) Combined use of the adenosine A(2A) antagonist KW-6002 with l-DOPA or with selective D₁ or D₂ dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys. Exp Neurol 162:321–327. https://doi.org/10.1006/exnr.2000.7350 PubMedCrossRef

Ko WKD, Li Q, Cheng LY et al (2017) A preclinical study on the combined effects of repeated eltoprazine and preladenant treatment for alleviating l-DOPA-induced dyskinesia in Parkinson’s disease. Eur J Pharmacol 813:10–16. https://doi.org/10.1016/j.ejphar.2017.07.030 PubMedCrossRef

Koga K, Kurokawa M, Ochi M et al (2000) Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats. Eur J Pharmacol 408:249–255. https://doi.org/10.1016/S0014-2999(00)00745-7 PubMedCrossRef

Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, Winsky-Sommerer R, Semba K, Fredholm BB, Boison D, Hayaishi O, Urade Y, Chen JF (2011) Arousal effect of caffeine depends on adenosine A_2A receptors in the shell of the nucleus accumbens. J Neurosci 31:10067–10075. https://doi.org/10.1523/JNEUROSCI.6730-10.2011 PubMedPubMedCentralCrossRef

Lewitt PA, Guttman M, Tetrud JW et al (2008) Adenosine A_2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol 63:295–302. https://doi.org/10.1002/ana.21315 PubMedCrossRef

Łukasiewicz S, Blasiak E, Faron-Gorecka A et al (2007) Fluorescence studies of homooligomerization of adenosine A_2A and serotonin 5-HT1A receptors reveal the specificity of receptor interactions in the plasma membrane. Pharmacol Rep 59:379–392PubMed

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. https://doi.org/10.1046/j.0953-816x.2001.01843.x PubMedCrossRef

Lundblad M, Vaudano E, Cenci MA (2003) Cellular and behavioural effects of the adenosine A_2a receptor antagonist KW-6002 in a rat model of l-DOPA-induced dyskinesia. J Neurochem 84:1398–1410. https://doi.org/10.1046/j.1471-4159.2003.01632.x PubMedCrossRef

Marin C, Aguilar E, Bonastre M et al (2005) Early administration of entacapone prevents levodopa-induced motor fluctuations in hemiparkinsonian rats. Exp Neurol 192:184–193. https://doi.org/10.1016/j.expneurol.2004.10.008 PubMedCrossRef

Meredith GE, Kang UJ (2006) Behavioral models of Parkinson’s disease in rodents: a new look at an old problem. Mov Disord 21:1595–1606. https://doi.org/10.1002/mds.21010 PubMedCrossRef

Morelli M, Di Paolo T, Wardas J et al (2007) Role of adenosine A_2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. Prog Neurobiol 83:293–309. https://doi.org/10.1016/j.pneurobio.2007.07.001 PubMedCrossRef

Morelli M, Blandini F, Simola N, Hauser RA (2012) A(2A) receptor antagonism and dyskinesia in Parkinson’s disease. Parkinsons Dis 2012:489853. https://doi.org/10.1155/2012/489853 PubMedPubMedCentralCrossRef

Muñoz A, Li Q, Gardoni F et al (2008) Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of l-DOPA-induced dyskinesia. Brain 131:3380–3394. https://doi.org/10.1093/brain/awn235 PubMedCrossRef

Navailles S, De Deurwaerdère P (2011) Presynaptic control of serotonin on striatal dopamine function. Psychopharmacology 213:213–242. https://doi.org/10.1007/s00213-010-2029-y PubMedCrossRef

Navarro G, Carriba P, Gandía J et al (2008) Detection of heteromers formed by cannabinoid CB₁, dopamine D₂, and adenosine A_2A G-protein-coupled receptors by combining bimolecular fluorescence complementation and bioluminescence energy transfer. Sci World J 8:1088–1097. https://doi.org/10.1100/tsw.2008.136 CrossRef

Nevalainen N, Bjerkén S, Gerhardt GA, Strömberg I (2014) Serotonergic nerve fibers in l-DOPA-derived dopamine release and dyskinesia. Neuroscience 260:73–86. https://doi.org/10.1016/j.neuroscience.2013.12.029 PubMedCrossRef

Obeso JA, Rodríguez-Oroz MC, Rodríguez M et al (2000) Pathophysiology of the basal ganglia in Parkinson’s disease. Trends Neurosci 23:S8–S19. https://doi.org/10.1016/S1471-1931(00)00028-8 PubMedCrossRef

Obeso JA, Rodriguez-Oroz M, Marin C et al (2004) The origin of motor fluctuations in Parkinson’s disease: importance of dopaminergic innervation and basal ganglia circuits. Neurology 62:S17–S30PubMedCrossRef

Ochi M, Shiozaki S, Kase H (2004) Adenosine A(2A) receptor-mediated modulation of GABA and glutamate release in the output regions of the basal ganglia in a rodent model of Parkinson’s disease. Neuroscience 127:223–231. https://doi.org/10.1016/j.neuroscience.2004.04.050 PubMedCrossRef

Oh JD, Chase TN (2002) Glutamate-mediated striatal dysregulation and the pathogenesis of motor response complications in Parkinson’s disease. Amino Acids 23:133–139. https://doi.org/10.1007/s00726-001-0118-2 PubMedCrossRef

Ohno Y, Shimizu S, Tokudome K et al (2015) New insight into the therapeutic role of the serotonergic system in Parkinson’s disease. Prog Neurobiol 134:104–121. https://doi.org/10.1016/j.pneurobio.2015.09.005 PubMedCrossRef

Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 22:123–144. https://doi.org/10.1146/annurev.neuro.22.1.123 PubMedCrossRef

Olanow CW, Damier P, Goetz CG et al (2004) Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). Clin Neuropharmacol 27:58–62. https://doi.org/10.1097/00002826-200403000-00003 PubMedCrossRef

Olanow CW, Stern MB, Sethi K (2009) The scientific and clinical basis for the treatment of Parkinson disease. Neurology 72:S1–S136. https://doi.org/10.1212/WNL.0b013e3181a1d44c PubMedCrossRef

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. https://doi.org/10.1016/0006-8993(94)90796-X PubMedCrossRef

Pascual O, Casper KB, Kubera C et al (2005) Astrocytic purinergic signalling coordinates synaptic networks. Science 310:113–116. https://doi.org/10.1126/science.1116916 PubMedCrossRef

Pedata F, Dettori I, Coppi E et al (2016) Purinergic signalling in brain ischemia. Neuropharmacology 104:105–130. https://doi.org/10.1016/j.neuropharm.2015.11.007 PubMedCrossRef

Pinna A (2014) Adenosine A_2A receptor antagonists in Parkinson’s disease: progress in clinical trials from the newly approved istradefylline to drugs in early development and those already discontinued. CNS Drugs 28:455–474. https://doi.org/10.1007/s40263-014-0161-7 PubMedCrossRef

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; A(2A) receptor antagonists. Neurotox Res 25:392–401. https://doi.org/10.1007/s12640-013-9446-8 PubMedCrossRef

Pinna A, Fenu S, Morelli M (2001) Motor stimulant effects of the adenosine A_2A receptor antagonist SCH 58261 do not develop tolerance after repeated treatments in 6-hydroxydopamine-lesioned rats. Synapse 39:233–238. https://doi.org/10.1002/1098-2396(20010301)39:3<233::aid-syn1004>3.0.co;2-k CrossRefPubMed

Pinna A, Wardas J, Simola N, Morelli M (2005) New therapies for the treatment of Parkinson’s disease: adenosine A_2A receptor antagonists. Life Sci 77:3259–3267. https://doi.org/10.1016/j.lfs.2005.04.029 PubMedCrossRef

Pinna A, Pontis S, Borsini F, Morelli M (2007) Adenosine A_2A receptor antagonists improve deficits in initiation of movement and sensory motor integration in the unilateral 6-hydroxydopamine rat model of Parkinson’s disease. Synapse 61:606–614. https://doi.org/10.1002/syn.20410 PubMedCrossRef

Pinna A, Tronci E, Schintu N et al (2010) A new ethyladenine antagonist of adenosine A(2A) receptors: behavioral and biochemical characterization as an antiparkinsonian drug. Neuropharmacology 58:613–623. https://doi.org/10.1016/j.neuropharm.2009.11.012 PubMedCrossRef

Pinna A, Bonaventura J, Farré D et al (2014) l-DOPA disrupts adenosine A(2A)-cannabinoid CB(1)-dopamine D(2) receptor heteromer cross-talk in the striatum of hemiparkinsonian rats: biochemical and behavioral studies. Exp Neurol 253:180–191. https://doi.org/10.1016/j.expneurol.2013.12.021 PubMedCrossRef

Pinna A, Ko WK, Costa G et al (2016) Antidyskinetic effect of A_2A and 5HT1A/1B receptor ligands in two animal models of Parkinson’s disease. Mov Disord 31:501–511. https://doi.org/10.1002/mds.26475 PubMedCrossRef

Politis M, Wu K, Loane C et al (2010) Serotonergic neurons mediate dyskinesia side effects in Parkinson’s patients with neural transplants. Sci Transl Med 2:38–46. https://doi.org/10.1126/scitranslmed.3000976 CrossRef

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. https://doi.org/10.1172/JCI71640 PubMedCrossRef

Popoli P, Pepponi R (2012) Potential therapeutic relevance of adenosine A₂B and A_2A receptors in the central nervous system. CNS Neurol Disord Drug Targets 11:664–674. https://doi.org/10.2174/187152712803581100 PubMedCrossRef

Rascol O, Perez-Lloret S, Ferreira JJ (2015) New treatments for levodopa-induced motor complications. Mov Disord 30:1451–1460. https://doi.org/10.1002/mds.26362 PubMedCrossRef

Rebola N, Canas PM, Oliveira CR, Cunha RA (2005) Different synaptic and subsynaptic localization of adenosine A_2A receptors in the hippocampus and striatum of the rat. Neuroscience 132:893–903. https://doi.org/10.1016/j.neuroscience.2005.01.014 PubMedCrossRef

Rivkees SA, Thevananther S, Hao H (2000) Are A₃ adenosine receptors expressed in the brain? NeuroReport 11:1025–1030PubMedCrossRef

Rodrigues RJ, Alfaro TM, Rebola N et al (2005) Colocalization and functional interaction between adenosine A(2A) and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J Neurochem 92:433–441. https://doi.org/10.1111/j.1471-4159.2004.02887.x PubMedCrossRef

Rose S, Jackson MJ, Smith LA et al (2006) The novel adenosine A_2a receptor antagonist ST1535 potentiates the effects of a threshold dose of l-DOPA in MPTP treated common marmosets. Eur J Pharmacol 546:82–87. https://doi.org/10.1016/j.ejphar.2006.07.017 PubMedCrossRef

Rosin DL, Robeva A, Woodard RL et al (1998) Immunohistochemical localization of adenosine A_2A receptors in the rat central nervous system. J Comp Neurol 401:163–186. https://doi.org/10.1002/(sici)1096-9861(19981116)401:2<163::aid-cne2>3.0.co;2-d PubMedCrossRef

Salamone JD, Betz AJ, Ishiwari K et al (2008) Tremorolytic effects of adenosine A_2A antagonists: implications for parkinsonism. Front Biosci 13:3594–3605. https://doi.org/10.2741/2952 PubMedCrossRef

Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18:435–450. https://doi.org/10.1038/nrn.2017.62 PubMedCrossRef

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 57:1062–1067. https://doi.org/10.1111/j.1471-4159.1991.tb08257.x PubMedCrossRef

Schwarzschild MA, Agnati L, Fuxe K et al (2006) Targeting adenosine A_2A receptors in Parkinson’s disease. Trends Neurosci 29:647–654. https://doi.org/10.1016/j.tins.2006.09.004 PubMedCrossRef

Sebastião AM, Ribeiro JA (2009) Adenosine receptors and the central nervous system. Handb Exp Pharmacol 193:471–534. https://doi.org/10.1007/978-3-540-89615-9_16 CrossRef

Shindou T, Mori A, Kase H, Ichimura M (2001) Adenosine A(2A) receptor enhances GABA(A)-mediated IPSCs in the rat globus pallidus. J Physiol 532:423–434. https://doi.org/10.1111/j.1469-7793.2001.0423f.x PubMedPubMedCentralCrossRef

Simola N, Fenu S, Baraldi PG et al (2004) Blockade of adenosine A_2A receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions. Exp Neurol 189:182–188. https://doi.org/10.1016/j.expneurol.2004.05.027 PubMedCrossRef

Simola N, Fenu S, Baraldi PG et al (2006a) Involvement of globus pallidus in the antiparkinsonian effects of adenosine A(2A) receptor antagonists. Exp Neurol 202:255–257. https://doi.org/10.1016/j.expneurol.2006.05.015 PubMedCrossRef

Simola N, Fenu S, Baraldi PG et al (2006b) Dopamine and adenosine receptor interaction as basis for the treatment of Parkinson’s disease. J Neurol Sci 248:48–52. https://doi.org/10.1016/j.jns.2006.05.038 PubMedCrossRef

Simola N, Morelli M, Pinna A (2008a) Adenosine A_2A receptor antagonists and Parkinson’s disease: state of the art and future directions. Curr Pharm Des 14:1475–1489. https://doi.org/10.2174/138161208784480072 PubMedCrossRef

Simola N, Fenu S, Baraldi PG et al (2008b) Blockade of globus pallidus adenosine A(2A) receptors displays antiparkinsonian activity in 6-hydroxydopamine-lesioned rats treated with D(1) or D(2) dopamine receptor agonists. Synapse 62:345–351. https://doi.org/10.1002/syn.20504 PubMedCrossRef

Simola N, Costa G, Morelli M (2016) Activation of adenosine A_2A receptors suppresses the emission of pro-social and drug-stimulated 50-kHz ultrasonic vocalizations in rats: possible relevance to reward and motivation. Psychopharmacology 233:507–519. https://doi.org/10.1007/s00213-015-4130-8 PubMedCrossRef

Stacy M, Silver D, Mendis T et al (2008) A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease. Neurology 70:2233–2240. https://doi.org/10.1212/01.wnl.0000313834.22171.17 PubMedCrossRef

Stayte S, Vissel B (2014) Advances in non-dopaminergic treatments for Parkinson’s disease. Front Neurosci 8:113. https://doi.org/10.3389/fnins.2014.00113 PubMedPubMedCentralCrossRef

Svenningsson P, Le Moine C, Aubert I, Burbaud P, Fredholm BB, Bloch B (1998) Cellular distribution of adenosine A_2A receptor mRNA in the primate striatum. J Comp Neurol 399:229–240. https://doi.org/10.1002/(sici)1096-9861(19980921)399:2<229::aid-cne6>3.0.co;2-2 PubMedCrossRef

Svenningsson P, Rosenblad C, Af Edholm Arvidsson K et al (2015) Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study. Brain 138:963–973. https://doi.org/10.1093/brain/awu409 PubMedPubMedCentralCrossRef

Tronci E, Simola N, Borsini F et al (2007) Characterization of the antiparkinsonian effects of the new adenosine A_2A receptor antagonist ST1535: acute and subchronic studies in rats. Eur J Pharmacol 566:94–102. https://doi.org/10.1016/j.ejphar.2007.03.021 PubMedCrossRef

Varty GB, Hodgson RA, Pond AJ et al (2008) The effects of adenosine A_2A receptor antagonists on haloperidol-induced movement disorders in primates. Psychopharmacology 200:393–401. https://doi.org/10.1007/s00213-008-1214-8 PubMedCrossRef

Wardas J (2003) Synergistic effect of SCH 58261, an adenosine A_2A receptor antagonist, and l-DOPA on the reserpine-induced muscle rigidity in rats. Pol J Pharmacol 55:155–164PubMed

Wardas J, Konieczny J, Lorenc-Koci E (2001) SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats. Synapse 41:160–171. https://doi.org/10.1002/syn.1070 PubMedCrossRef

Xiao D, Bastia E, Xu YH et al (2006) Forebrain adenosine A_2A receptors contribute to l-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice. J Neurosci 26:13548–13555. https://doi.org/10.1523/JNEUROSCI.3554-06.2006 PubMedCrossRef

Yamada H, Aimi Y, Nagatsu I et al (2007) Immunohistochemical detection of l-DOPA-derived dopamine within serotonergic fibers in the striatum and the substantia nigra pars reticulata in Parkinsonian model rats. Neurosci Res 59:1–7. https://doi.org/10.1016/j.neures.2007.05.002 PubMedCrossRef

Titel: Role of adenosine A2A receptors in motor control: relevance to Parkinson’s disease and dyskinesia
verfasst von: Annalisa Pinna
Marcello Serra
Micaela Morelli
Nicola Simola
Publikationsdatum: 02.02.2018
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 8/2018
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-018-1848-6

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