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The Adenosine Receptor: A Homeostatic Neuromodulator for Fine-Tuning Control of Cognition

  • Jiang-Fan Chen
Chapter
Part of the The Receptors book series (REC, volume 34)

Abstract

There is a convergence of neurochemical studies showing the dual roles of neuromodulation and homeostatic function by adenosine receptors (AR), with animal studies demonstrating the strong pro-cognitive impact upon AR antagonism in healthy and diseased brains, with the epidemiological evidence in support of caffeine and AR drugs used for the therapeutic modulation of cognition. This perspective led to the proposal that the adenosine and AR may uniquely position to modulate cognitive behaviors in normal and disease conditions. This review first describes the ability of AR to integrate dopamine and glutamate signaling and to modulate synaptic plasticity by acting through the inhibitory A1 and facilitating A2A receptors (A2AR). It is followed by the discussion on the animal studies demonstrating the strong pro-cognitive effects of AR (mainly the A2A receptor) antagonism on a variety of cognitive behaviors. These studies reveal several novel insights into the mechanism underlying AR control of cognition: temporally precise interaction of adenosine with dopamine and glutamate signaling at the striatum, striatopallidal A2ARs function as a common “break” mechanism to constrain cognition, and selective modulation of distinct phases of working memory information processing. We further describe the evidence for the aberrantly increased adenosine-AR signaling under pathological conditions. Accordingly, blocking the aberrant AR signaling reverses cognitive impairments in animal models of neurodegenerative disorders. AR modification of neurodegenerative proteins (including α-synuclein, β-amyloid, and phosphorylation of Tau) and neuroprotection against synaptic loss are discussed as the potential mechanisms underlying AR control of cognitive deficits. Last, translational potential of A2AR antagonists and caffeine for cognitive improvement is highlighted with non-human primate studies and epidemiological findings. As caffeine is regularly consumed by >50% world population and A2AR antagonists are in phase III clinical trials for Parkinson’s disease with noted safety profiles, this convergence of molecular, animal, and epidemiological evidence supporting AR control of cognition will stimulate necessary clinical investigations to explore AR-targeting drugs as a novel strategy to ameliorate cognitive deficits in neuropsychiatric disorders.

Keywords

Adenosine receptors Cognition modulation A1R antagonism A2AR antagonism Neuropsychiatric disorders Caffeine 

References

  1. Aarsland D, Bronnick K, Williams-Gray C et al (2010) Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology 75(12):1062–1069PubMedPubMedCentralCrossRefGoogle Scholar
  2. Airan RD, Thompson KR, Fenno LE (2009) Temporally precise in vivo control of intracellular signalling. Nature 458(7241):1025–1029CrossRefPubMedGoogle Scholar
  3. Aisen PS, Cummings J, Schneider LS (2012) Symptomatic and nonamyloid/tau based pharmacologic treatment for Alzheimer disease. Cold Spring Harb Perspect Med 2(3):a006395PubMedPubMedCentralCrossRefGoogle Scholar
  4. Albasanz JL, Perez S, Barrachina M et al (2008) Up-regulation of adenosine receptors in the frontal cortex in Alzheimer’s disease. Brain Pathol 18(2):211–219PubMedCrossRefGoogle Scholar
  5. Albert MS (1996) Cognitive and neurobiologic markers of early Alzheimer disease. Proc Natl Acad Sci U S A 93(24):13547–13551PubMedPubMedCentralCrossRefGoogle Scholar
  6. Amanzio M, Benedetti F, Vase L (2012) A systematic review of adverse events in the placebo arm of donepezil trials: the role of cognitive impairment. Int Psychogeriatr 24(5):698–707PubMedCrossRefGoogle Scholar
  7. Andreasen N, Minthon L, Davidsson P et al (2001) Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol 58(3):373–379PubMedCrossRefGoogle Scholar
  8. Aquili L, Liu AW, Shindou M et al (2014) Behavioral flexibility is increased by optogenetic inhibition of neurons in the nucleus accumbens shell during specific time segments. Learn Mem 21(4):223–231PubMedPubMedCentralCrossRefGoogle Scholar
  9. Arendash GW, Schleif W, Rezai-Zadeh K et al (2006) Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience 142(4):941–952PubMedCrossRefGoogle Scholar
  10. Arendash GW, Mori T, Cao C et al (2009) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer’s disease mice. J Alzheimers Dis 17(3):661–680PubMedCrossRefPubMedCentralGoogle Scholar
  11. Augustin SM, Beeler JA, McGehee DS et al (2014) Cyclic AMP and afferent activity govern bidirectional synaptic plasticity in striatopallidal neurons. J Neurosci 34(19):6692–6699PubMedPubMedCentralCrossRefGoogle Scholar
  12. Augusto E, Matos M, Sevigny J et al (2013) Ecto-5′-nucleotidase (CD73)-mediated formation of adenosine is critical for the striatal adenosine A2A receptor functions. J Neurosci 33(28):11390–11399PubMedPubMedCentralCrossRefGoogle Scholar
  13. Baddeley A (2003) Working memory: looking back and looking forward. Nat Rev Neurosci 4(10):829–839PubMedCrossRefGoogle Scholar
  14. Baddeley AD, Bressi S, Della Sala S et al (1991) The decline of working memory in Alzheimer’s disease. A longitudinal study. Brain J Neurol 114(6):2521–2542CrossRefGoogle Scholar
  15. Ballarin M, Fredholm BB, Ambrosio S et al (1991) Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism. Acta Physiol Scand 142(1):97–103CrossRefPubMedGoogle Scholar
  16. Bastia E, Xu YH, Scibelli AC et al (2005) A crucial role for forebrain adenosine A(2A) receptors in amphetamine sensitization. Neuropsychopharmacology 30(5):891–900PubMedCrossRefGoogle Scholar
  17. Batalha VL, Ferreira DG, Coelho JE et al (2016) The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function. Sci Rep 6:31493PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bateup HS, Santini E, Shen W et al (2010) Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors. Proc Natl Acad Sci U S A 107(33):14845–14850PubMedPubMedCentralCrossRefGoogle Scholar
  19. Belleville S, Sylvain-Roy S, de Boysson C et al (2008) Characterizing the memory changes in persons with mild cognitive impairment. Prog Brain Res 169:365–375PubMedCrossRefGoogle Scholar
  20. Blundon JA, Bayazitov IT, Zakharenko SS (2011) Presynaptic gating of postsynaptically expressed plasticity at mature thalamocortical synapses. J Neurosci 31(44):16012–16025PubMedPubMedCentralCrossRefGoogle Scholar
  21. Boison D (2011) Modulators of nucleoside metabolism in the therapy of brain diseases. Curr Top Med Chem 11(8):1068–1086PubMedPubMedCentralCrossRefGoogle Scholar
  22. Boyden ES, Zhang F, Bamberg E et al (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263–1268PubMedCrossRefGoogle Scholar
  23. Brainard MS, Doupe AJ (2000) Interruption of a basal ganglia-forebrain circuit prevents plasticity of learned vocalizations. Nature 404(6779):762–766PubMedCrossRefGoogle Scholar
  24. Brundege JM, Dunwiddie TV (1998) Metabolic regulation of endogenous adenosine release from single neurons. Neuroreport 9(13):3007–3011PubMedCrossRefGoogle Scholar
  25. Brundin P, Melki R (2017) Prying into the prion hypothesis for Parkinson’s disease. J Neurosci 37(41):9808–9818PubMedPubMedCentralCrossRefGoogle Scholar
  26. Burgos-Robles A, Bravo-Rivera H, Quirk GJ (2013) Prelimbic and infralimbic neurons signal distinct aspects of appetitive instrumental behavior. PLoS One 8(2):e57575PubMedPubMedCentralCrossRefGoogle Scholar
  27. Burke SN, Barnes CA (2010) Senescent synapses and hippocampal circuit dynamics. Trends Neurosci 33(3):153–161PubMedPubMedCentralCrossRefGoogle Scholar
  28. Canals M, Marcellino D, Fanelli F et al (2003) Adenosine A2A-dopamine D2 receptor-receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 278(47):46741–46749PubMedCrossRefPubMedCentralGoogle Scholar
  29. Canas PM, Porciuncula LO, Cunha GM et al (2009a) Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway. J Neurosci 29(47):14741–14751PubMedCrossRefGoogle Scholar
  30. Canas PM, Duarte JM, Rodrigues RJ et al (2009b) Modification upon aging of the density of presynaptic modulation systems in the hippocampus. Neurobiol Aging 30(11):1877–1884PubMedCrossRefGoogle Scholar
  31. Cao C, Cirrito JR, Lin X et al (2009) Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer’s disease transgenic mice. J Alzheimers Dis 17(3):681–697PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cao C, Loewenstein DA, Lin X et al (2012) High blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimers Dis 30(3):559–572PubMedPubMedCentralCrossRefGoogle Scholar
  33. Chamberlain SE, Sadowski JH, Teles-Grilo Ruivo LM et al (2013) Long-term depression of synaptic kainate receptors reduces excitability by relieving inhibition of the slow after hyperpolarization. J Neurosci 33(22):9536–9545PubMedPubMedCentralCrossRefGoogle Scholar
  34. Chaudhuri KR, Schapira AH (2009) Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8(5):464–474PubMedCrossRefGoogle Scholar
  35. Chekeni FB, Elliott MR, Sandilos JK et al (2010) Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature 467(7317):863–867PubMedPubMedCentralCrossRefGoogle Scholar
  36. Chen JF (2014) Adenosine receptor control of cognition in normal and disease. Int Rev Neurobiol 119:257–307PubMedCrossRefPubMedCentralGoogle Scholar
  37. Chen Y, Corriden R, Inoue Y et al (2006) ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science 314(5806):1792–1795PubMedCrossRefPubMedCentralGoogle Scholar
  38. Chen JF, Eltzschig HK, Fredholm BB (2013) Adenosine receptors as drug targets--what are the challenges? Nat Rev Drug Discov 12(4):265–286PubMedPubMedCentralCrossRefGoogle Scholar
  39. Chiang MC, Chen HM, Lai HL et al (2009) The A2A adenosine receptor rescues the urea cycle deficiency of Huntington’s disease by enhancing the activity of the ubiquitin-proteasome system. Hum Mol Genet 18(16):2929–2942PubMedCrossRefPubMedCentralGoogle Scholar
  40. Chung HJ, Ge WP, Qian X et al (2009) G protein-activated inwardly rectifying potassium channels mediate depotentiation of long-term potentiation. Proc Natl Acad Sci U S A 106(2):635–640PubMedCrossRefGoogle Scholar
  41. Ciruela F, Casado V, Rodrigues RJ et al (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci 26(7):2080–2087PubMedCrossRefPubMedCentralGoogle Scholar
  42. Coccurello R, Breysse N, Amalric M (2004) Simultaneous blockade of adenosine A2A and metabotropic glutamate mGlu5 receptors increase their efficacy in reversing Parkinsonian deficits in rats. Neuropsychopharmacology 29(8):1451–1461PubMedCrossRefGoogle Scholar
  43. Cognato GP, Agostinho PM, Hockemeyer J et al (2010) Caffeine and an adenosine A(2A) receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life. J Neurochem 112(2):453–462PubMedCrossRefGoogle Scholar
  44. Coleman P, Federoff H, Kurlan R (2004) A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology 63(7):1155–1162PubMedCrossRefGoogle Scholar
  45. Correa M, Pardo M, Bayarri P et al (2016) Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A(2)AKO mice. Psychopharmacology 233(3):393–404PubMedCrossRefGoogle Scholar
  46. 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(2):107–125PubMedCrossRefPubMedCentralGoogle Scholar
  47. Cunha RA (2008a) Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity. Neurochem Int 52(1–2):65–72PubMedCrossRefGoogle Scholar
  48. Cunha RA (2008b) Caffeine, adenosine receptors, memory and Alzheimer disease. Med Clin (Barc) 131(20):790–795CrossRefGoogle Scholar
  49. Cunha RA, Agostinho PM (2010) Chronic caffeine consumption prevents memory disturbance in different animal models of memory decline. J Alzheimers Dis 20(Suppl 1):S95–S116Google Scholar
  50. Cunha RA, Constantino MC, Sebastiao AM et al (1995) Modification of A1 and A2a adenosine receptor binding in aged striatum, hippocampus and cortex of the rat. Neuroreport 6(11):1583–1588PubMedCrossRefGoogle Scholar
  51. Cunha RA, Correia-de-Sa P, Sebastiao AM et al (1996) Preferential activation of excitatory adenosine receptors at rat hippocampal and neuromuscular synapses by adenosine formed from released adenine nucleotides. Br J Pharmacol 119(2):253–260PubMedPubMedCentralCrossRefGoogle Scholar
  52. Cunha RA, Almeida T, Ribeiro JA (2001) Parallel modification of adenosine extracellular metabolism and modulatory action in the hippocampus of aged rats. J Neurochem 76(2):372–382PubMedCrossRefGoogle Scholar
  53. Cunha GM, Canas PM, Oliveira CR et al (2006) Increased density and synapto-protective effect of adenosine A2A receptors upon sub-chronic restraint stress. Neuroscience 141(4):1775–1781PubMedCrossRefGoogle Scholar
  54. Cunha RA, Ferre S, Vaugeois JM et al (2008) Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders. Curr Pharm Des 14(15):1512–1524PubMedPubMedCentralCrossRefGoogle Scholar
  55. D’Alcantara P, Ledent C, Swillens S et al (2001) Inactivation of adenosine A2A receptor impairs long term potentiation in the accumbens nucleus without altering basal synaptic transmission. Neuroscience 107(3):455–464PubMedCrossRefGoogle Scholar
  56. Dall’Igna OP, Fett P, Gomes MW et al (2007) Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice. Exp Neurol 203(1):241–245PubMedCrossRefGoogle Scholar
  57. de Mendonca A, Ribeiro JA (1997) Adenosine and neuronal plasticity. Life Sci 60(4–5):245–251PubMedGoogle Scholar
  58. Deisseroth K (2014) Circuit dynamics of adaptive and maladaptive behaviour. Nature 505(7483):309–317PubMedPubMedCentralCrossRefGoogle Scholar
  59. Dennissen FJ, Anglada-Huguet M, Sydow A et al (2016) Adenosine A1 receptor antagonist rolofylline alleviates axonopathy caused by human tau DeltaK280. Proc Natl Acad Sci U S A 113(41):11597–11602PubMedPubMedCentralCrossRefGoogle Scholar
  60. Desmurget M, Turner RS (2010) Motor sequences and the basal ganglia: kinematics, not habits. J Neurosci 30(22):7685–7690PubMedPubMedCentralCrossRefGoogle Scholar
  61. Dias RB, Ribeiro JA, Sebastiao AM (2012) Enhancement of AMPA currents and GluR1 membrane expression through PKA-coupled adenosine A(2A) receptors. Hippocampus 22(2):276–291PubMedCrossRefPubMedCentralGoogle Scholar
  62. Dias RB, Rombo DM, Ribeiro JA et al (2013) Adenosine: setting the stage for plasticity. Trends Neurosci 36(4):248–257PubMedCrossRefGoogle Scholar
  63. Diogenes MJ, Neves-Tome R, Fucile S et al (2014) Homeostatic control of synaptic activity by endogenous adenosine is mediated by adenosine kinase. Cereb Cortex 24(1):67–80PubMedCrossRefGoogle Scholar
  64. Dixon AK, Gubitz AK, Sirinathsinghji DJ et al (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118(6):1461–1468PubMedPubMedCentralCrossRefGoogle Scholar
  65. Dungo R, Deeks ED (2013) Istradefylline: first global approval. Drugs 73(8):875–882PubMedCrossRefGoogle Scholar
  66. Dunwiddie TV, Fredholm BB (1997) In: Jacobson KA, Jarvis MF (eds) Purinergic approaches in experimental therapeutics. Wiley-Liss, New York, pp 359–382Google Scholar
  67. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55PubMedCrossRefGoogle Scholar
  68. Durieux PF, Bearzatto B, Guiducci S et al (2009) D2R striatopallidal neurons inhibit both locomotor and drug reward processes. Nat Neurosci 12(4):393–395PubMedCrossRefGoogle Scholar
  69. Durieux PF, Schiffmann SN, de Kerchove d’Exaerde A (2012) Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions. EMBO J 31(3):640–653PubMedCrossRefGoogle Scholar
  70. Elliott MR, Chekeni FB, Trampont PC et al (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461(7261):282–286PubMedPubMedCentralCrossRefGoogle Scholar
  71. Eltzschig HK (2009) Adenosine: an old drug newly discovered. Anesthesiology 111(4):904–915PubMedPubMedCentralCrossRefGoogle Scholar
  72. Ena SL, De Backer JF, Schiffmann SN et al (2013) FACS array profiling identifies Ecto-5′ nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning. J Neurosci 33(20):8794–8809PubMedCrossRefGoogle Scholar
  73. Eskelinen MH, Ngandu T, Tuomilehto J et al (2009) Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis 16(1):85–91PubMedCrossRefGoogle Scholar
  74. Espinosa J, Rocha A, Nunes F et al (2013) Caffeine consumption prevents memory impairment, neuronal damage, and adenosine A2A receptors upregulation in the hippocampus of a rat model of sporadic dementia. J Alzheimers Dis 34(2):509–518PubMedCrossRefGoogle Scholar
  75. Ewers M, Walsh C, Trojanowski JQ et al (2012) Prediction of conversion from mild cognitive impairment to Alzheimer’s disease dementia based upon biomarkers and neuropsychological test performance. Neurobiol Aging 33(7):1203–1214PubMedCrossRefGoogle Scholar
  76. Faigle M, Seessle J, Zug S et al (2008) ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia. PLoS One 3(7):e2801PubMedPubMedCentralCrossRefGoogle Scholar
  77. Farrell MS, Pei Y, Wan Y et al (2013) A Galphas DREADD mouse for selective modulation of cAMP production in striatopallidal neurons. Neuropsychopharmacology 38(5):854–862PubMedPubMedCentralCrossRefGoogle Scholar
  78. Ferre S, Fredholm BB, Morelli M et al (1997) Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 20(10):482–487PubMedCrossRefGoogle Scholar
  79. Ferre S, Karcz-Kubicha M, Hope BT et al (2002) Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc Natl Acad Sci U S A 99(18):11940–11945PubMedPubMedCentralCrossRefGoogle Scholar
  80. Ferre S, Quiroz C, Woods AS et al (2008) An update on adenosine A2A-dopamine D2 receptor interactions: implications for the function of G protein-coupled receptors. Curr Pharm Des 14(15):1468–1474PubMedPubMedCentralCrossRefGoogle Scholar
  81. Ferre S, Lluis C, Justinova Z et al (2010) Adenosine-cannabinoid receptor interactions. Implications for striatal function. Br J Pharmacol 160(3):443–453PubMedPubMedCentralCrossRefGoogle Scholar
  82. Ferreira DG, Batalha VL, Vicente Miranda H et al (2017) Adenosine A2A receptors modulate alpha-Synuclein aggregation and toxicity. Cereb Cortex 27(1):718–730PubMedGoogle Scholar
  83. Ferretti V, Roullet P, Sargolini F et al (2010) Ventral striatal plasticity and spatial memory. Proc Natl Acad Sci U S A 107(17):7945–7950PubMedPubMedCentralCrossRefGoogle Scholar
  84. Fink JS, Weaver DR, Rivkees SA et al (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):186–195PubMedCrossRefGoogle Scholar
  85. Flajolet M, Wang Z, Futter M et al (2008) FGF acts as a co-transmitter through adenosine A(2A) receptor to regulate synaptic plasticity. Nat Neurosci 11(12):1402–1409PubMedPubMedCentralCrossRefGoogle Scholar
  86. Floresco SB, Seamans JK, Phillips AG (1997) Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay. J Neurosci 17(5):1880–1890PubMedCrossRefGoogle Scholar
  87. Fontinha BM, Diogenes MJ, Ribeiro JA et al (2008) Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. Neuropharmacology 54(6):924–933PubMedCrossRefGoogle Scholar
  88. Fontinha BM, Delgado-Garcia JM, Madronal N et al (2009) Adenosine A(2A) receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice. Neuropsychopharmacology 34(7):1865–1874PubMedCrossRefGoogle Scholar
  89. Fredholm BB (2007) Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ 14(7):1315–1323CrossRefPubMedGoogle Scholar
  90. Fredholm BB, Chen JF, Cunha RA et al (2005a) Adenosine and brain function. Int Rev Neurobiol 63:191–270PubMedCrossRefGoogle Scholar
  91. Fredholm B, Chen JF, Masino SA et al (2005b) Actions of adenosine at its receptors in the CNS: insights from knockouts and drugs. Annu Rev Pharmacol Toxicol 45:385–412PubMedCrossRefGoogle Scholar
  92. Fredholm BB, AP IJ, 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):1–34PubMedPubMedCentralCrossRefGoogle Scholar
  93. Fuxe K, Agnati LF, Jacobsen K et al (2003) Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson’s disease. Neurology 61(11):S19–S23PubMedPubMedCentralCrossRefGoogle Scholar
  94. Galasko D, Chang L, Motter R et al (1998) High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. Arch Neurol 55(7):937–945PubMedCrossRefGoogle Scholar
  95. Gelber RP, Petrovitch H, Masaki KH et al (2011) Coffee intake in midlife and risk of dementia and its neuropathologic correlates. J Alzheimers Dis 23(4):607–615PubMedPubMedCentralCrossRefGoogle Scholar
  96. Gengler S, Mallot HA, Holscher C (2005) Inactivation of the rat dorsal striatum impairs performance in spatial tasks and alters hippocampal theta in the freely moving rat. Behav Brain Res 164(1):73–82PubMedCrossRefGoogle Scholar
  97. Gerevich Z, Wirkner K, Illes P (2002) Adenosine A2A receptors inhibit the N-methyl-D-aspartate component of excitatory synaptic currents in rat striatal neurons. Eur J Pharmacol 451(2):161–164PubMedCrossRefGoogle Scholar
  98. Giguere PM, Kroeze WK, Roth BL (2014) Tuning up the right signal: chemical and genetic approaches to study GPCR functions. Curr Opin Cell Biol 27:51–55PubMedCrossRefGoogle Scholar
  99. Gimenez-Llort L, Fernandez-Teruel A, Escorihuela RM et al (2002) Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur J Neurosci 16(3):547–550PubMedCrossRefGoogle Scholar
  100. Gimenez-Llort L, Masino SA, Diao L et al (2005) Mice lacking the adenosine A(1) receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly. Synapse 57(1):8–16PubMedPubMedCentralCrossRefGoogle Scholar
  101. Gimenez-Llort L, Schiffmann SN, Shmidt T et al (2007) Working memory deficits in transgenic rats overexpressing human adenosine A2A receptors in the brain. Neurobiol Learn Mem 87(1):42–56PubMedCrossRefGoogle Scholar
  102. Goedert M, Masuda-Suzukake M, Falcon B (2017) Like prions: the propagation of aggregated tau and alpha-synuclein in neurodegeneration. Brain J Neurol 140(2):266–278CrossRefGoogle Scholar
  103. Goldman-Rakic PS (1987) Development of cortical circuitry and cognitive function. Child Dev 58(3):601–622PubMedCrossRefGoogle Scholar
  104. Gomes CV, Kaster MP, Tome AR et al (2011) Adenosine receptors and brain diseases: neuroprotection and neurodegeneration. Biochim Biophys Acta 1808(5):1380–1399PubMedCrossRefGoogle Scholar
  105. Grady CL, Furey ML, Pietrini P et al (2001) Altered brain functional connectivity and impaired short-term memory in Alzheimer’s disease. Brain J Neurol 124(Pt 4):739–756CrossRefGoogle Scholar
  106. Gunaydin LA, Grosenick L, Finkelstein JC et al (2014) Natural neural projection dynamics underlying social behavior. Cell 157(7):1535–1551PubMedPubMedCentralCrossRefGoogle Scholar
  107. Halassa MM, Fellin T, Takano H et al (2007) Synaptic islands defined by the territory of a single astrocyte. J Neurosci 27(24):6473–6477PubMedCrossRefGoogle Scholar
  108. Halassa MM, Florian C, Fellin T et al (2009) Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61(2):213–219PubMedPubMedCentralCrossRefGoogle Scholar
  109. Hallock HL, Arreola AC, Shaw CL et al (2013) Dissociable roles of the dorsal striatum and dorsal hippocampus in conditional discrimination and spatial alternation T-maze tasks. Neurobiol Learn Mem 100:108–116PubMedCrossRefGoogle Scholar
  110. Hameleers PA, Van Boxtel MP, Hogervorst E et al (2000) Habitual caffeine consumption and its relation to memory, attention, planning capacity and psychomotor performance across multiple age groups. Hum Psychopharmacol 15(8):573–581PubMedCrossRefGoogle Scholar
  111. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356PubMedCrossRefGoogle Scholar
  112. 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(3):221–229PubMedCrossRefGoogle Scholar
  113. Higley MJ, Sabatini BL (2010) Competitive regulation of synaptic Ca2+ influx by D2 dopamine and A2A adenosine receptors. Nat Neurosci 13(8):958–966PubMedPubMedCentralCrossRefGoogle Scholar
  114. Hikida T, Yawata S, Yamaguchi T et al (2013) Pathway-specific modulation of nucleus accumbens in reward and aversive behavior via selective transmitter receptors. Proc Natl Acad Sci U S A 110(1):342–347PubMedCrossRefGoogle Scholar
  115. Hillion J, Canals M, Torvinen M et al (2002) Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 277(20):18091–18097PubMedCrossRefPubMedCentralGoogle Scholar
  116. Hooper N, Fraser C, Stone TW (1996) Effects of purine analogues on spontaneous alternation in mice. Psychopharmacology 123(3):250–257PubMedCrossRefGoogle Scholar
  117. Horgusluoglu-Moloch E, Nho K, Risacher SL et al (2017) Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 60:92–103PubMedCrossRefGoogle Scholar
  118. Hu Q, Ren X, Liu Y et al (2016) Aberrant adenosine A2A receptor signaling contributes to neurodegeneration and cognitive impairments in a mouse model of synucleinopathy. Exp Neurol 283(Pt A):213–223PubMedCrossRefGoogle Scholar
  119. Huang CL, Yang JM, Wang KC et al (2011) Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A(2)A receptor and ubiquitin proteasome system. J Ethnopharmacol 138(1):162–168PubMedCrossRefPubMedCentralGoogle Scholar
  120. Ito R, Robbins TW, Pennartz CM et al (2008) Functional interaction between the hippocampus and nucleus accumbens shell is necessary for the acquisition of appetitive spatial context conditioning. J Neurosci 28(27):6950–6959PubMedPubMedCentralCrossRefGoogle Scholar
  121. Jenner P, Mori A, Hauser R et al (2009) Adenosine, adenosine A 2A antagonists, and Parkinson’s disease. Parkinsonism Relat Disord 15(6):406–413PubMedCrossRefGoogle Scholar
  122. Johansson B, Halldner L, Dunwiddie TV et al (2001) Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor. Proc Natl Acad Sci U S A 98(16):9407–9412PubMedPubMedCentralCrossRefGoogle Scholar
  123. Johnson A, van der Meer MA, Redish AD (2007) Integrating hippocampus and striatum in decision-making. Curr Opin Neurobiol 17(6):692–697PubMedCrossRefGoogle Scholar
  124. Jones RW (2010) A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors. Int J Geriatr Psychiatry 25(6):547–553PubMedGoogle Scholar
  125. Justinova Z, Redhi GH, Goldberg SR et al (2014) Differential effects of presynaptic versus postsynaptic adenosine A2A receptor blockade on Delta9-tetrahydrocannabinol (THC) self-administration in squirrel monkeys. J Neurosci 34(19):6480–6484PubMedPubMedCentralCrossRefGoogle Scholar
  126. Kachroo A, Schwarzschild MA (2012) Adenosine A2A receptor gene disruption protects in an alpha-synuclein model of Parkinson’s disease. Ann Neurol 71(2):278–282PubMedPubMedCentralCrossRefGoogle Scholar
  127. Kachroo A, Orlando LR, Grandy DK et al (2005) Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice. J Neurosci 25(45):10414–10419PubMedCrossRefPubMedCentralGoogle Scholar
  128. Kadowaki Horita T, Kobayashi M, Mori A et al (2013) Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex. Psychopharmacology 230(3):345–352PubMedCrossRefGoogle Scholar
  129. Kamikubo Y, Shimomura T, Fujita Y et al (2013) Functional cooperation of metabotropic adenosine and glutamate receptors regulates postsynaptic plasticity in the cerebellum. J Neurosci 33(47):18661–18671PubMedCrossRefGoogle Scholar
  130. Kardani J, Roy I (2015) Understanding Caffeine’s role in attenuating the toxicity of alpha-Synuclein aggregates: implications for risk of Parkinson’s disease. ACS Chem Neurosci 6(9):1613–1625PubMedCrossRefGoogle Scholar
  131. Kaster MP, Machado NJ, Silva HB et al (2015) Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress. Proc Natl Acad Sci U S A 112(25):7833–7838PubMedPubMedCentralCrossRefGoogle Scholar
  132. Kellendonk C, Simpson EH, Polan HJ et al (2006) Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 49(4):603–615PubMedCrossRefGoogle Scholar
  133. Kerr MI, Wall MJ, Richardson MJ (2013) Adenosine A1 receptor activation mediates the developmental shift at layer 5 pyramidal cell synapses and is a determinant of mature synaptic strength. J Physiol 591(Pt 13):3371–3380PubMedPubMedCentralCrossRefGoogle Scholar
  134. Khanapur S, Waarde A, Ishiwata K et al (2014) Adenosine A(2A) receptor antagonists as positron emission tomography (PET) tracers. Curr Med Chem 21(3):312–328PubMedCrossRefPubMedCentralGoogle Scholar
  135. Kim CS, Johnston D (2015) A1 adenosine receptor-mediated GIRK channels contribute to the resting conductance of CA1 neurons in the dorsal hippocampus. J Neurophysiol 113(7):2511–2523PubMedPubMedCentralCrossRefGoogle Scholar
  136. King AE, Ackley MA, Cass CE et al (2006) Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol Sci 27(8):416–425PubMedCrossRefPubMedCentralGoogle Scholar
  137. Kirsch GE, Codina J, Birnbaumer L et al (1990) Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes. Am J Phys 259(3):H820–H826Google Scholar
  138. Klyuch BP, Dale N, Wall MJ (2012) Deletion of ecto-5′-nucleotidase (CD73) reveals direct action potential-dependent adenosine release. J Neurosci 32(11):3842–3847PubMedCrossRefGoogle Scholar
  139. Ko WKD, Camus SM, Li Q et al (2016) An evaluation of istradefylline treatment on Parkinsonian motor and cognitive deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque models. Neuropharmacology 110(Pt A):48–58PubMedCrossRefGoogle Scholar
  140. Kopf SR, Melani A, Pedata F, Pepeu G (1999) Adenosine and memory storage: effect of A(1) and A(2) receptor antagonists. Psychopharmacology 146(2):214–219PubMedCrossRefGoogle Scholar
  141. Koppel J, Sunday S, Goldberg TE et al (2014) Psychosis in Alzheimer’s disease is associated with frontal metabolic impairment and accelerated decline in working memory: findings from the Alzheimer’s disease neuroimaging initiative. Am J Geriatr Psychiatry 22(7):698–707PubMedCrossRefGoogle Scholar
  142. Krania P, Dimou E, Bantouna M et al (2018) Adenosine A2A receptors are required for glutamate mGluR5- and dopamine D1 receptor-evoked ERK1/2 phosphorylation in rat hippocampus: involvement of NMDA receptor. J Neurochem. https://doi.org/10.1111/jnc.14268
  143. Kukley M, Schwan M, Fredholm BB et al (2005) The role of extracellular adenosine in regulating mossy fiber synaptic plasticity. J Neurosci 25(11):2832–2837PubMedCrossRefGoogle Scholar
  144. Landau SM, Harvey D, Madison CM et al (2010) Comparing predictors of conversion and decline in mild cognitive impairment. Neurology 75(3):230–238PubMedPubMedCentralCrossRefGoogle Scholar
  145. Lang UE, Lang F, Richter K et al (2003) Emotional instability but intact spatial cognition in adenosine receptor 1 knock out mice. Behav Brain Res 145(1–2):179–188PubMedCrossRefGoogle Scholar
  146. Larsson M, Sawada K, Morland C et al (2012) Functional and anatomical identification of a vesicular transporter mediating neuronal ATP release. Cereb Cortex 22(5):1203–1124PubMedCrossRefGoogle Scholar
  147. Laurent C, Burnouf S, Ferry B et al (2016) A2A adenosine receptor deletion is protective in a mouse model of Tauopathy. Mol Psychiatry 21(1):97–107PubMedCrossRefPubMedCentralGoogle Scholar
  148. Lazarus M, Shen HY, Cherasse Y et al (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 31(27):10067–10075PubMedPubMedCentralCrossRefGoogle Scholar
  149. Lerner TN, Horne EA, Stella N et al (2010) Endocannabinoid signaling mediates psychomotor activation by adenosine A2A antagonists. J Neurosci 30(6):2160–2164PubMedPubMedCentralCrossRefGoogle Scholar
  150. Li YC, Kellendonk C, Simpson EH et al (2011) D2 receptor overexpression in the striatum leads to a deficit in inhibitory transmission and dopamine sensitivity in mouse prefrontal cortex. Proc Natl Acad Sci U S A 108(29):12107–12112PubMedPubMedCentralCrossRefGoogle Scholar
  151. Li P, Rial D, Canas PM et al (2015a) Optogenetic activation of intracellular adenosine A2A receptor signaling in the hippocampus is sufficient to trigger CREB phosphorylation and impair memory. Mol Psychiatry 20(11):1339–1349PubMedPubMedCentralCrossRefGoogle Scholar
  152. Li W, Silva HB, Real J et al (2015b) Inactivation of adenosine A2A receptors reverses working memory deficits at early stages of Huntington’s disease models. Neurobiol Dis 79:70–80PubMedCrossRefPubMedCentralGoogle Scholar
  153. Li Y, He Y, Chen M et al (2016) Optogenetic activation of adenosine A2A receptor signaling in the Dorsomedial Striatopallidal neurons suppresses goal-directed behavior. Neuropsychopharmacology 41(4):1003–1013PubMedCrossRefGoogle Scholar
  154. Li Z, Chen X, Wang T et al (2018) The corticostriatal adenosine A2A receptor controls maintenance and retrieval of working memory. Biol Psychiatry 83(6):530–541Google Scholar
  155. Liljeholm M, O’Doherty JP (2012) Contributions of the striatum to learning, motivation, and performance: an associative account. Trends Cogn Sci 16(9):467–475PubMedPubMedCentralCrossRefGoogle Scholar
  156. Linden J (2006) Purinergic chemotaxis. Science 314(5806):1689–1690PubMedCrossRefGoogle Scholar
  157. Lindsay J, Laurin D, Verreault R et al (2002) Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian study of health and aging. Am J Epidemiol 156(5):445–453PubMedCrossRefGoogle Scholar
  158. Liu D, Gu X, Zhu J et al (2014) Medial prefrontal activity during delay period contributes to learning of a working memory task. Science 346(6208):458–463PubMedCrossRefGoogle Scholar
  159. Lobo MK, Cui Y, Ostlund SB et al (2007) Genetic control of instrumental conditioning by striatopallidal neuron-specific S1P receptor Gpr6. Nat Neurosci 10(11):1395–1397PubMedCrossRefGoogle Scholar
  160. Lobo MK, Covington HE 3rd, Chaudhury D et al (2010) Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science 330(6002):385–390PubMedPubMedCentralCrossRefGoogle Scholar
  161. Londos C, Cooper DM, Wolff J (1980) Subclasses of external adenosine receptors. Proc Natl Acad Sci U S A 77(5):2551–2554PubMedPubMedCentralCrossRefGoogle Scholar
  162. Lopes LV, Cunha RA, Ribeiro JA (1999a) Cross talk between A(1) and A(2A) adenosine receptors in the hippocampus and cortex of young adult and old rats. J Neurophysiol 82(6):3196–3203PubMedCrossRefPubMedCentralGoogle Scholar
  163. Lopes LV, Cunha RA, Ribeiro JA (1999b) Increase in the number, G protein coupling, and efficiency of facilitatory adenosine A2A receptors in the limbic cortex, but not striatum, of aged rats. J Neurochem 73(4):1733–1738PubMedCrossRefPubMedCentralGoogle Scholar
  164. Lopes LV, Cunha RA, Kull B et al (2002) Adenosine A(2A) receptor facilitation of hippocampal synaptic transmission is dependent on tonic A(1) receptor inhibition. Neuroscience 112(2):319–329PubMedCrossRefPubMedCentralGoogle Scholar
  165. Lovatt D, Xu Q, Liu W et al (2012) Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity. Proc Natl Acad Sci U S A 109(16):6265–6270PubMedPubMedCentralCrossRefGoogle Scholar
  166. Lovinger DM, Choi S (1995) Activation of adenosine A1 receptors initiates short-term synaptic depression in rat striatum. Neurosci Lett 199(1):9–12PubMedCrossRefGoogle Scholar
  167. Lu G, Zhou QX, Kang S et al (2010) Chronic morphine treatment impaired hippocampal long-term potentiation and spatial memory via accumulation of extracellular adenosine acting on adenosine A1 receptors. J Neurosci 30(14):5058–5070PubMedCrossRefGoogle Scholar
  168. MacAskill AF, Little JP, Cassel JM, Carter AG (2012) Subcellular connectivity underlies pathway-specific signaling in the nucleus accumbens. Nat Neurosci 15(12):1624–1626PubMedPubMedCentralCrossRefGoogle Scholar
  169. MacDonald PE, Braun M, Galvanovskis J et al (2006) Release of small transmitters through kiss-and-run fusion pores in rat pancreatic beta cells. Cell Metab 4(4):283–290PubMedCrossRefGoogle Scholar
  170. Machado NJ, Simoes AP, Silva HB et al (2017) Caffeine reverts memory but not mood impairment in a depression-prone mouse strain with up-regulated adenosine A2A receptor in hippocampal glutamate synapses. Mol Neurobiol 54(2):1552–1563PubMedCrossRefPubMedCentralGoogle Scholar
  171. Maldonado-Irizarry CS, Kelley AE (1995) Excitatory amino acid receptors within nucleus accumbens subregions differentially mediate spatial learning in the rat. Behavioural pharmacology 6(5 And 6):527–539PubMedGoogle Scholar
  172. Marquez-Ruiz J, Leal-Campanario R, Sanchez-Campusano R et al (2012) Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits. Proc Natl Acad Sci U S A 109(17):6710–6715PubMedPubMedCentralCrossRefGoogle Scholar
  173. Martire A, Tebano MT, Chiodi V et al (2011) Pre-synaptic adenosine A2A receptors control cannabinoid CB1 receptor-mediated inhibition of striatal glutamatergic neurotransmission. J Neurochem 116(2):273–280PubMedCrossRefGoogle Scholar
  174. Masuda-Suzukake M, Nonaka T, Hosokawa M et al (2013) Prion-like spreading of pathological alpha-synuclein in brain. Brain J Neurol 136(Pt 4):1128–1138CrossRefGoogle Scholar
  175. Matos M, Shen HY, Augusto E et al (2015) Deletion of adenosine A2A receptors from astrocytes disrupts glutamate homeostasis leading to psychomotor and cognitive impairment: relevance to schizophrenia. Biol Psychiatry 78(11):763–774PubMedPubMedCentralCrossRefGoogle Scholar
  176. Matthews RT, Coker O, Winder DG (2004) A novel mouse brain slice preparation of the hippocampo-accumbens pathway. J Neurosci Methods 137(1):49–60PubMedCrossRefGoogle Scholar
  177. Mattsson N, Zetterberg H, Hansson O et al (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302(4):385–393PubMedCrossRefGoogle Scholar
  178. McDonald RJ, Jones J, Richards B et al (2006) A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum. Eur J Neurosci 24(6):1789–1801PubMedCrossRefGoogle Scholar
  179. Mingote S, Font L, Farrar AM et al (2008) Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway. J Neurosci 28(36):9037–9046PubMedPubMedCentralCrossRefGoogle Scholar
  180. Mishina M, Ishiwata K, Naganawa M et al (2011) Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson’s disease patients. PLoS One 6(2):e17338PubMedPubMedCentralCrossRefGoogle Scholar
  181. Moore KA, Nicoll RA, Schmitz D (2003) Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses. Proc Natl Acad Sci U S A 100(24):14397–11402PubMedPubMedCentralCrossRefGoogle Scholar
  182. Mori A, Shindou T (2003) Modulation of GABAergic transmission in the striatopallidal system by adenosine A2A receptors: a potential mechanism for the antiparkinsonian effects of A2A antagonists. Neurology 61(11 Suppl 6):S44–S48PubMedCrossRefGoogle Scholar
  183. Morrison JH, Baxter MG (2012) The ageing cortical synapse: hallmarks and implications for cognitive decline. Nat Rev Neurosci 13(4):240–250PubMedPubMedCentralCrossRefGoogle Scholar
  184. Mott AM, Nunes EJ, Collins LE et al (2009) The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure. Psychopharmacology 204(1):103–112PubMedPubMedCentralCrossRefGoogle Scholar
  185. Mouro FM, Batalha VL, Ferreira DG et al (2017) Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation. Neuropharmacology 117:316–327PubMedCrossRefGoogle Scholar
  186. Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet 349(9064):1498–1504CrossRefPubMedGoogle Scholar
  187. Nam HW, Hinton DJ, Kang NY et al (2013) Adenosine transporter ENT1 regulates the acquisition of goal-directed behavior and ethanol drinking through A2A receptor in the dorsomedial striatum. J Neurosci 33(10):4329–4338PubMedPubMedCentralCrossRefGoogle Scholar
  188. Ning YL, Yang N, Chen X et al (2013) Adenosine A2A receptor deficiency alleviates blast-induced cognitive dysfunction. J Cereb Blood Flow Metab 33(11):1789–1798PubMedPubMedCentralCrossRefGoogle Scholar
  189. O’Neill M, Brown VJ (2007) Amphetamine and the adenosine A(2A) antagonist KW-6002 enhance the effects of conditional temporal probability of a stimulus in rats. Behav Neurosci 121(3):535–542PubMedCrossRefGoogle Scholar
  190. Ohno M, Watanabe S (1996) Working memory failure by stimulation of hippocampal adenosine A1 receptors in rats. Neuroreport 7(18):3013–3016PubMedCrossRefGoogle Scholar
  191. Olesen J, Gustavsson A, Svensson M et al (2012) The economic cost of brain disorders in Europe. Eur J Neurol 19(1):155–162PubMedCrossRefGoogle Scholar
  192. Oliveros A, Cho CH, Cui A et al (2017) Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation. Transl Psychiatry 7(4):e1095PubMedPubMedCentralCrossRefGoogle Scholar
  193. Ongini E, Fredholm BB (1996) Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci 17(10):364–372PubMedPubMedCentralCrossRefGoogle Scholar
  194. Orr AG, Hsiao EC, Wang MM et al (2015) Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat Neurosci 18(3):423–434PubMedPubMedCentralCrossRefGoogle Scholar
  195. Orr AG, Lo I, Schumacher H et al (2018) Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol Dis 110:29–36PubMedCrossRefGoogle Scholar
  196. Pagnussat N, Almeida AS, Marques DM et al (2015) Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice. Br J Pharmacol 172(15):3831–3845PubMedPubMedCentralCrossRefGoogle Scholar
  197. Pardo M, Lopez-Cruz L, Valverde O et al (2012) Adenosine A2A receptor antagonism and genetic deletion attenuate the effects of dopamine D2 antagonism on effort-based decision making in mice. Neuropharmacology 62(5–6):2068–2077PubMedCrossRefGoogle Scholar
  198. Pennartz CM, Ito R, Verschure PF et al (2011) The hippocampal-striatal axis in learning, prediction and goal-directed behavior. Trends Neurosci 34(10):548–559PubMedCrossRefGoogle Scholar
  199. Pereira GS, Rossato JI, Sarkis JJ et al (2005) Activation of adenosine receptors in the posterior cingulate cortex impairs memory retrieval in the rat. Neurobiol Learn Mem 83(3):217–223PubMedCrossRefGoogle Scholar
  200. Pereira M, Farrar AM, Hockemeyer J et al (2011) Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat. Psychopharmacology 213(1):69–79PubMedCrossRefGoogle Scholar
  201. Piray P (2011) The role of dorsal striatal D2-like receptors in reversal learning: a reinforcement learning viewpoint. J Neurosci 31(40):14049–14050PubMedCrossRefGoogle Scholar
  202. Pomata PE, Belluscio MA, Riquelme LA (2008) NMDA receptor gating of information flow through the striatum in vivo. J Neurosci 28(50):13384–13389PubMedCrossRefGoogle Scholar
  203. Postuma RB, Anang J, Pelletier A et al (2017) Caffeine as symptomatic treatment for Parkinson disease (Cafe-PD): a randomized trial. Neurology 89(17):1795–1803PubMedCrossRefGoogle Scholar
  204. Prediger RD, Takahashi RN (2005) Modulation of short-term social memory in rats by adenosine A1 and A(2A) receptors. Neurosci Lett 376(3):160–165PubMedCrossRefGoogle Scholar
  205. Prediger RD, Fernandes D, Takahashi RN (2005a) Blockade of adenosine A2A receptors reverses short-term social memory impairments in spontaneously hypertensive rats. Behav Brain Res 159(2):197–205PubMedCrossRefGoogle Scholar
  206. Prediger RD, Pamplona FA, Fernandes D et al (2005b) Caffeine improves spatial learning deficits in an animal model of attention deficit hyperactivity disorder (ADHD) – the spontaneously hypertensive rat (SHR). Int J Neuropsychopharmacol 8(4):583–594PubMedCrossRefGoogle Scholar
  207. Ramlackhansingh AF, Bose SK, Ahmed I et al (2011) Adenosine 2A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease. Neurology 76(21):1811–1816PubMedPubMedCentralCrossRefGoogle Scholar
  208. Rebola N, Sebastiao AM, de Mendonca A et al (2003) Enhanced adenosine A2A receptor facilitation of synaptic transmission in the hippocampus of aged rats. J Neurophysiol 90(2):1295–1303PubMedCrossRefGoogle Scholar
  209. Rebola N, Rodrigues RJ, Lopes LV et al (2005a) Adenosine A1 and A2A receptors are co-expressed in pyramidal neurons and co-localized in glutamatergic nerve terminals of the rat hippocampus. Neuroscience 133(1):79–83PubMedCrossRefGoogle Scholar
  210. Rebola N, Canas PM, Oliveira CR et al (2005b) Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat. Neuroscience 132(4):893–903PubMedCrossRefGoogle Scholar
  211. Rebola N, Lujan R, Cunha RA et al (2008) Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses. Neuron 57(1):121–134PubMedCrossRefGoogle Scholar
  212. Reppert SM, Weaver DR, Stehle JH et al (1991) Molecular cloning and characterization of a rat A1-adenosine receptor that is widely expressed in brain and spinal cord. Mol Endocrinol 5(8):1037–1048PubMedCrossRefGoogle Scholar
  213. Resta R, Yamashita Y, Thompson LF (1998) Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev 161:95–109PubMedCrossRefGoogle Scholar
  214. Reynolds JN, Hyland BI, Wickens JR (2001) A cellular mechanism of reward-related learning. Nature 413(6851):67–70PubMedCrossRefGoogle Scholar
  215. Ribeiro JA (1999) Adenosine A2A receptor interactions with receptors for other neurotransmitters and neuromodulators. Eur J Pharmacol 375(1–3):101–113PubMedCrossRefGoogle Scholar
  216. Ribeiro JA, Sebastiao AM, de Mendonca A (2002) Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol 68(6):377–392PubMedCrossRefGoogle Scholar
  217. Richard IH, Justus AW, Greig NH et al (2002) Worsening of motor function and mood in a patient with Parkinson’s disease after pharmacologic challenge with oral rivastigmine. Clin Neuropharmacol 25(6):296–299PubMedCrossRefGoogle Scholar
  218. Riemenschneider M, Lautenschlager N, Wagenpfeil S et al (2002) Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment. Arch Neurol 59(11):1729–1734PubMedCrossRefGoogle Scholar
  219. Ritchie K, Carrière I, Portet F et al (2007) The neuro-protective effects of caffeine: a prospective population study (the three City study). Neurology 69(6):536–545PubMedCrossRefGoogle Scholar
  220. Rodrigues RJ, Alfaro TM, Rebola N et al (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):433–441PubMedCrossRefGoogle Scholar
  221. Rosin DL, Hettinger BD, Lee A et al (2003) Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function. Neurology 61(11):S12–S18PubMedCrossRefGoogle Scholar
  222. Sandau US, Colino-Oliveira M, Jones A et al (2016) Adenosine kinase deficiency in the brain results in maladaptive synaptic plasticity. J Neurosci 36(48):12117–12128PubMedPubMedCentralCrossRefGoogle Scholar
  223. Sarantis K, Tsiamaki E, Kouvaros S et al (2015) Adenosine A(2)A receptors permit mGluR5-evoked tyrosine phosphorylation of NR2B (Tyr1472) in rat hippocampus: a possible key mechanism in NMDA receptor modulation. J Neurochem 135(4):714–726PubMedCrossRefGoogle Scholar
  224. Scammell TE, Arrigoni E, Thompson MA et al (2003) Focal deletion of the adenosine A1 receptor in adult mice using an adeno-associated viral vector. J Neurosci 23(13):5762–5770PubMedCrossRefGoogle Scholar
  225. Scanziani M, Capogna M, Gahwiler BH (1992) Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron 9(5):919–927PubMedCrossRefPubMedCentralGoogle Scholar
  226. Scheff SW, Price DA, Schmitt FA et al (2007) Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 68(18):1501–1508PubMedCrossRefGoogle Scholar
  227. Schiffmann SN, Vanderhaeghen JJ (1993) Adenosine A2 receptors regulate the gene expression of striatopallidal and striatonigral neurons. J Neurosci 13(3):1080–1087PubMedCrossRefPubMedCentralGoogle Scholar
  228. Schiffmann SN, Fisone G, Moresco R et al (2007) Adenosine A2A receptors and basal ganglia physiology. Prog Neurobiol 83(5):277–292PubMedPubMedCentralCrossRefGoogle Scholar
  229. Schmitt LI, Sims RE, Dale N et al (2012) Wakefulness affects synaptic and network activity by increasing extracellular astrocyte-derived adenosine. J Neurosci 32(13):4417–4425PubMedPubMedCentralCrossRefGoogle Scholar
  230. Schotanus SM, Fredholm BB, Chergui K (2006) NMDA depresses glutamatergic synaptic transmission in the striatum through the activation of adenosine A1 receptors: evidence from knockout mice. Neuropharmacology 51(2):272–282PubMedCrossRefGoogle Scholar
  231. Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275(5306):1593–1599PubMedCrossRefGoogle Scholar
  232. Scimeca JM, Badre D (2012) Striatal contributions to declarative memory retrieval. Neuron 75(3):380–392PubMedPubMedCentralCrossRefGoogle Scholar
  233. Seamans JK, Phillips AG (1994) Selective memory impairments produced by transient lidocaine-induced lesions of the nucleus accumbens in rats. Behav Neurosci 108(3):456–468PubMedCrossRefGoogle Scholar
  234. Sebastiao AM, Ribeiro JA (1996) Adenosine A2 receptor-mediated excitatory actions on the nervous system. Prog Neurobiol 48(3):167–189PubMedCrossRefGoogle Scholar
  235. Sebastiao AM, Ribeiro JA (2000) Fine-tuning neuromodulation by adenosine. Trends Pharmacol Sci 21(9):341–346PubMedCrossRefGoogle Scholar
  236. Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298(5594):789–791PubMedCrossRefPubMedCentralGoogle Scholar
  237. Shen HY, Coelho JE, Ohtsuka N et al (2008a) A critical role of the adenosine A2A receptor in extrastriatal neurons in modulating psychomotor activity as revealed by opposite phenotypes of striatum and forebrain A2A receptor knock-outs. J Neurosci 28(12):2970–2975PubMedCrossRefGoogle Scholar
  238. Shen W, Flajolet M, Greengard P et al (2008b) Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321(5890):848–851PubMedPubMedCentralCrossRefGoogle Scholar
  239. Shen HY, Canas PM, Garcia-Sanz P et al (2013) Adenosine A(2)A receptors in striatal glutamatergic terminals and GABAergic neurons oppositely modulate psychostimulant action and DARPP-32 phosphorylation. PLoS One 8(11):e80902PubMedPubMedCentralCrossRefGoogle Scholar
  240. Simoes AP, Machado NJ, Goncalves N et al (2016) Adenosine A2A receptors in the amygdala control synaptic plasticity and contextual fear memory. Neuropsychopharmacology 41(12):2862–2871PubMedPubMedCentralCrossRefGoogle Scholar
  241. Simpson EH, Kellendonk C, Kandel E et al (2010) A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 65(5):585–596PubMedPubMedCentralCrossRefGoogle Scholar
  242. Singer P, Wei CJ, Chen JF et al (2013) Deletion of striatal adenosine A(2A) receptor spares latent inhibition and prepulse inhibition but impairs active avoidance learning. Behav Brain Res 242:54–61PubMedCrossRefGoogle Scholar
  243. Spellman T, Rigotti M, Ahmari SE et al (2015) Hippocampal-prefrontal input supports spatial encoding in working memory. Nature 522(7556):309–314PubMedPubMedCentralCrossRefGoogle Scholar
  244. Sperling RA, Dickerson BC, Pihlajamaki M et al (2010) Functional alterations in memory networks in early Alzheimer’s disease. NeuroMolecular Med 12(1):27–43PubMedPubMedCentralCrossRefGoogle Scholar
  245. Tai LH, Lee AM, Benavidez N et al (2012) Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value. Nat Neurosci 15(9):1281–1289PubMedPubMedCentralCrossRefGoogle Scholar
  246. Tebano MT, Martire A, Potenza RL et al (2008) Adenosine A(2A) receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus. J Neurochem 104(1):279–286PubMedGoogle Scholar
  247. Todd KJ, Darabid H, Robitaille R (2010) Perisynaptic glia discriminate patterns of motor nerve activity and influence plasticity at the neuromuscular junction. J Neurosci 30(35):11870–11182PubMedCrossRefGoogle Scholar
  248. Tyebji S, Saavedra A, Canas PM et al (2015) Hyperactivation of D1 and A2A receptors contributes to cognitive dysfunction in Huntington’s disease. Neurobiol Dis 74:41–57PubMedCrossRefPubMedCentralGoogle Scholar
  249. van Boxtel MP, Schmitt JA, Bosma H et al (2003) The effects of habitual caffeine use on cognitive change: a longitudinal perspective. Pharmacol Biochem Behav 75(4):921–927PubMedCrossRefGoogle Scholar
  250. van Calker D, Muller M, Hamprecht B (1978) Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells. Nature 276(5690):839–841PubMedCrossRefGoogle Scholar
  251. van der Meer MA, Redish AD (2011) Ventral striatum: a critical look at models of learning and evaluation. Curr Opin Neurobiol 21(3):387–392PubMedPubMedCentralCrossRefGoogle Scholar
  252. van Gelder BM, Buijsse B, Tijhuis M et al (2007) Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE study. Eur J Clin Nutr 61(2):226–232PubMedCrossRefPubMedCentralGoogle Scholar
  253. van Groen T, Wyss JM (1990) Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections. J Comp Neurol 302(3):515–528PubMedCrossRefGoogle Scholar
  254. van Laar T, De Deyn PP, Aarsland D et al (2011) Effects of cholinesterase inhibitors in Parkinson’s disease dementia: a review of clinical data. CNS Neurosci Ther 17(5):428–441PubMedCrossRefGoogle Scholar
  255. Villar-Menendez I, Porta S, Buira SP et al (2014) Increased striatal adenosine A2A receptor levels is an early event in Parkinson’s disease-related pathology and it is potentially regulated by miR-34b. Neurobiol Dis 69:206–214PubMedCrossRefGoogle Scholar
  256. Walsh DM, Selkoe DJ (2004) Deciphering the molecular basis of memory failure in Alzheimer’s disease. Neuron 44(1):181–193PubMedCrossRefGoogle Scholar
  257. Wan Q, Yao H, Wang F (1999) Involvement of K(+) channels in the inhibitory effects of adenosine on anoxia-induced [Ca(2+) ](i) increase in cultured rat hippocampal CA1 neurons. Biol Signals Recept 8(4–5):309–315PubMedCrossRefGoogle Scholar
  258. Wang JH, Ma YY, van den Buuse M (2006) Improved spatial recognition memory in mice lacking adenosine A2A receptors. Exp Neurol 199(2):438–445PubMedCrossRefGoogle Scholar
  259. Wei CJ, Li W, Chen JF (2011a) Normal and abnormal functions of adenosine receptors in the central nervous system revealed by genetic knockout studies. Biochim Biophys Acta 1808(5):1358–1379PubMedCrossRefGoogle Scholar
  260. Wei CJ, Singer P, Coelho J et al (2011b) Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning. Learn Mem 18(7):459–474PubMedPubMedCentralCrossRefGoogle Scholar
  261. Wei C, Augusto E, Gomes C et al (2014) Regulation of fear responses by striatal and extra-striatal adenosine A2A receptors in forebrain. Biol Psychiatry 75(11):855–863PubMedCrossRefGoogle Scholar
  262. Weintraub S, Wicklund AH, Salmon DP (2012) The neuropsychological profile of Alzheimer disease. Cold Spring Harb Perspect Med 2(4):a006171PubMedPubMedCentralCrossRefGoogle Scholar
  263. Wimo A, Jonsson L, Bond J et al (2013) The worldwide economic impact of dementia 2010. Alzheimers Dement 9(1):1–11e3PubMedCrossRefGoogle Scholar
  264. Wirkner K, Assmann H, Koles L et al (2000) Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. Br J Pharmacol 130(2):259–269PubMedPubMedCentralCrossRefGoogle Scholar
  265. Xia J, Chen F, Ye J et al (2009) Activity-dependent release of adenosine inhibits the glutamatergic synaptic transmission and plasticity in the hypothalamic hypocretin/orexin neurons. Neuroscience 162(4):980–988PubMedCrossRefGoogle Scholar
  266. Yagishita S, Hayashi-Takagi A, Ellis-Davies GC et al (2014) A critical time window for dopamine actions on the structural plasticity of dendritic spines. Science 345(6204):1616–1620PubMedPubMedCentralCrossRefGoogle Scholar
  267. Yamamoto J, Suh J, Takeuchi D et al (2014) Successful execution of working memory linked to synchronized high-frequency gamma oscillations. Cell 157(4):845–857PubMedCrossRefGoogle Scholar
  268. Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 1783(5):673–694PubMedCrossRefGoogle Scholar
  269. Yizhar O, Fenno LE, Davidson TJ et al (2011) Optogenetics in neural systems. Neuron 71(1):9–34PubMedCrossRefGoogle Scholar
  270. Yu L, Shen HY, Coelho JE et al (2008) Adenosine A2A receptor antagonists exert motor and neuroprotective effects by distinct cellular mechanisms. Ann Neurol 63(3):338–346PubMedCrossRefGoogle Scholar
  271. Yu C, Gupta J, Chen JF et al (2009) Genetic deletion of A2A adenosine receptors in the striatum selectively impairs habit formation. J Neurosci 29(48):15100–15103PubMedPubMedCentralCrossRefGoogle Scholar
  272. Zhang Z, Chen G, Zhou W et al (2007) Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 9(8):945–953PubMedCrossRefGoogle Scholar
  273. Zhao ZA, Li P, Ye SY et al (2017a) Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation. Sci Rep 7(1):2254PubMedPubMedCentralCrossRefGoogle Scholar
  274. Zhao ZA, Zhao Y, Ning YL et al (2017b) Adenosine A2A receptor inactivation alleviates early-onset cognitive dysfunction after traumatic brain injury involving an inhibition of tau hyperphosphorylation. Transl Psychiatry 7(5):e1123PubMedPubMedCentralCrossRefGoogle Scholar
  275. Zhou SJ, Zhu ME, Shu D et al (2009) Preferential enhancement of working memory in mice lacking adenosine A(2A) receptors. Brain Res 1303:74–83PubMedCrossRefGoogle Scholar
  276. Zimmermann H (2000) Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedeberg’s Arch Pharmacol 362(4–5):299–309CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Jiang-Fan Chen
    • 1
    • 2
  1. 1.The Molecular Neuropharmacology Laboratory, Wenzhou Medical UniversityWenzhou, ZhejiangPeople’s Republic of China
  2. 2.Department of NeurologyBoston University School of MedicineBostonUSA

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