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Dopamine and Wakefulness: Pharmacology, Genetics, and Circuitry

Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

Over the period of decades in the mid to late twentieth century, arousal-promoting functions were attributed to neuromodulators including serotonin, hypocretin, histamine, and noradrenaline. For some time, a relatively minor role in regulating sleep and wake states was ascribed to dopamine and the dopamine-producing cells of the ventral tegmental area, despite the fact that dopaminergic signaling is a major target, if not the primary target, for wake-promoting agents. In recent years, due to observations from human genetic studies, pharmacogenetic studies in animal models, and the increasingly sophisticated methods used to manipulate the nervous systems of experimental animals, it has become clear that dopaminergic signaling is central to the regulation of arousal. This chapter reviews this central role of dopaminergic signaling, and in particular its antagonistic interaction with adenosinergic signaling, in maintaining vigilance and in the response to wake-promoting therapeutics.

Keywords

Adenosine Basal ganglia Caffeine Dopamine Modafinil Nucleus accumbens Polymorphisms Sleep Stimulants Striatum 

References

  1. Abremski K, Hoess R (1984) Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. J Biol Chem 259:1509–1514PubMedGoogle Scholar
  2. Basheer R, Strecker RE, Thakkar MM, McCarley RW (2004) Adenosine and sleep-wake regulation. Prog Neurobiol 73:379–396CrossRefPubMedGoogle Scholar
  3. Blumenfeld H (2002) Basal ganglia. In: Blumenfeld H (ed) Neuroanatomy through clinical cases. Sinauer Associates, Sunderland, pp 689–735Google Scholar
  4. Bodenmann S, Xu S, Luhmann U, Arand M, Berger W, Jung H, Landolt H (2008) Pharmacogenetics of modafinil after sleep loss: catechol-O-methyltransferase genotype modulates waking functions but not recovery sleep. Clin Pharmacol Ther 85:296–304CrossRefPubMedGoogle Scholar
  5. Bodenmann S, Hohoff C, Freitag C, Deckert J, Retey JV, Bachmann V, Landolt HP (2012) Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation. Br J Pharmacol 165:1904–1913CrossRefPubMedPubMedCentralGoogle Scholar
  6. Braun AR, Balkin TJ, Wesenten NJ, Carson RE, Varga M, Baldwin P, Selbie S, Belenky G, Herscovitch P (1997) Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. Brain 120(Pt 7):1173–1197CrossRefPubMedGoogle Scholar
  7. Cade BE, Gottlieb DJ, Lauderdale DS, Bennett DA, Buchman AS, Buxbaum SG, De Jager PL, Evans DS, Fulop T, Gharib SA, Johnson WC, Kim H, Larkin EK, Lee SK, Lim AS, Punjabi NM, Shin C, Stone KL, Tranah GJ, Weng J, Yaffe K, Zee PC, Patel SR, Zhu X, Redline S, Saxena R (2016) Common variants in DRD2 are associated with sleep duration: the CARe consortium. Hum Mol Genet 25:167–179CrossRefPubMedGoogle Scholar
  8. Callaway CW, Henriksen SJ (1992) Neuronal firing in the nucleus accumbens is associated with the level of cortical arousal. Neuroscience 51:547–553CrossRefPubMedGoogle Scholar
  9. Dash MB, Douglas CL, Vyazovskiy VV, Cirelli C, Tononi G (2009) Long-term homeostasis of extracellular glutamate in the rat cerebral cortex across sleep and waking states. J Neurosci 29:620–629CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dauvilliers Y, Tafti M, Landolt HP (2015) Catechol-O-methyltransferase, dopamine, and sleep-wake regulation. Sleep Med Rev 22:47–53CrossRefPubMedGoogle Scholar
  11. de Saint Hilaire Z, Orosco M, Rouch C, Python A, Nicolaidis S (2000) Neuromodulation of the prefrontal cortex during sleep: a microdialysis study in rats. Neuroreport 11:1619–1624CrossRefPubMedGoogle Scholar
  12. Deisseroth K (2011) Optogenetics. Nat Methods 8:26–29CrossRefPubMedGoogle Scholar
  13. Dzirasa K, Ribeiro S, Costa R, Santos LM, Lin SC, Grosmark A, Sotnikova TD, Gainetdinov RR, Caron MG, Nicolelis MA (2006) Dopaminergic control of sleep-wake states. J Neurosci 26:10577–10589CrossRefPubMedGoogle Scholar
  14. Eban-Rothschild A, Rothschild G, Giardino WJ, Jones JR, de Lecea L (2016) VTA dopaminergic neurons regulate ethologically relevant sleep-wake behaviors. Nat Neurosci 19:1356–1366CrossRefPubMedPubMedCentralGoogle Scholar
  15. Faraone SV, Spencer TJ, Madras BK, Zhang-James Y, Biederman J (2014) Functional effects of dopamine transporter gene genotypes on in vivo dopamine transporter functioning: a meta-analysis. Mol Psychiatry 19:880–889CrossRefPubMedGoogle Scholar
  16. Fernandez-Duenas V, Gomez-Soler M, Lopez-Cano M, Taura JJ, Ledent C, Watanabe M, Jacobson KA, Vilardaga JP, Ciruela F (2014) Uncovering caffeine’s adenosine A2A receptor inverse agonism in experimental parkinsonism. ACS Chem Biol 9:2496–2501CrossRefPubMedPubMedCentralGoogle Scholar
  17. Garcia-Rill E, Heister DS, Ye M, Charlesworth A, Hayar A (2007) Novel mechanism for sleep-wake control: electrical coupling. Sleep 30:1405–1414CrossRefPubMedPubMedCentralGoogle Scholar
  18. Garzon M, Vaughan RA, Uhl GR, Kuhar MJ, Pickel VM (1999) Cholinergic axon terminals in the ventral tegmental area target a subpopulation of neurons expressing low levels of the dopamine transporter. J Comp Neurol 410:197–210CrossRefPubMedGoogle Scholar
  19. Gerashchenko D, Blanco-Centurion CA, Miller JD, Shiromani PJ (2006) Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137:29–36CrossRefPubMedGoogle Scholar
  20. Goel N, Banks S, Lin L, Mignot E, Dinges DF (2011) Catechol-O-methyltransferase Val158Met polymorphism associates with individual differences in sleep physiologic responses to chronic sleep loss. PLoS One 6:e29283ADSCrossRefPubMedPubMedCentralGoogle Scholar
  21. Gomez JL, Bonaventura J, Lesniak W, Mathews WB, Sysa-Shah P, Rodriguez LA, Ellis RJ, Richie CT, Harvey BK, Dannals RF, Pomper MG, Bonci A, Michaelides M (2017) Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. Science 357:503–507ADSCrossRefPubMedGoogle Scholar
  22. Gronli J, Clegern WC, Schmidt MA, Nemri RS, Rempe MJ, Gallitano AL, Wisor JP (2016) Sleep homeostatic and waking behavioral phenotypes in Egr3-deficient mice associated with serotonin receptor 5-HT2 deficits. Sleep 39:2189–2199CrossRefPubMedPubMedCentralGoogle Scholar
  23. Gujar N, Yoo SS, Hu P, Walker MP (2011) Sleep deprivation amplifies reactivity of brain reward networks, biasing the appraisal of positive emotional experiences. J Neurosci 31:4466–4474CrossRefPubMedPubMedCentralGoogle Scholar
  24. Holst SC, Bersagliere A, Bachmann V, Berger W, Achermann P, Landolt HP (2014) Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans. J Neurosci 34:566–573CrossRefPubMedGoogle Scholar
  25. Holst SC, Valomon A, Landolt HP (2016) Sleep pharmacogenetics: personalized sleep-wake therapy. Annu Rev Pharmacol Toxicol 56:577–603CrossRefPubMedGoogle Scholar
  26. Holst SC, Muller T, Valomon A, Seebauer B, Berger W, Landolt HP (2017) Functional polymorphisms in dopaminergic genes modulate neurobehavioral and neurophysiological consequences of sleep deprivation. Sci Rep 7:45982ADSCrossRefPubMedPubMedCentralGoogle Scholar
  27. Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8:858–859CrossRefPubMedGoogle Scholar
  28. Jones BE, Bobillier P, Pin C, Jouvet M (1973) The effect of lesions of catecholamine-containing neurons upon monoamine content of the brain and EEG and behavioral waking in the cat. Brain Res 58:157–177CrossRefPubMedGoogle Scholar
  29. Kim DS, Palmiter RD (2008) Interaction of dopamine and adenosine receptor function in behavior: studies with dopamine-deficient mice. Front Biosci 13:2311–2318CrossRefPubMedGoogle Scholar
  30. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM (1996) Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6:243–250CrossRefPubMedGoogle Scholar
  31. Landolt HP (2011) Genetic determination of sleep EEG profiles in healthy humans. Prog Brain Res 193:51–61CrossRefPubMedGoogle Scholar
  32. 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 A2A receptors in the shell of the nucleus accumbens. J Neurosci 31:10067–10075CrossRefPubMedPubMedCentralGoogle Scholar
  33. Lena I, Parrot S, Deschaux O, Muffat-Joly S, Sauvinet V, Renaud B, Suaud-Chagny MF, Gottesmann C (2005) Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep--wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats. J Neurosci Res 81:891–899CrossRefPubMedGoogle Scholar
  34. Lim J, Ebstein R, Tse CY, Monakhov M, Lai PS, Dinges DF, Kwok K (2012) Dopaminergic polymorphisms associated with time-on-task declines and fatigue in the psychomotor vigilance test. PLoS One 7:e33767ADSCrossRefPubMedPubMedCentralGoogle Scholar
  35. Liu Z, Wang Y, Cai L, Li Y, Chen B, Dong Y, Huang YH (2016) Prefrontal cortex to accumbens projections in sleep regulation of reward. J Neurosci 36:7897–7910CrossRefPubMedPubMedCentralGoogle Scholar
  36. Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, Kopajtic T, Shi L, Katz JL, Tanda G, Newman AH (2012) R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry 72:405–413CrossRefPubMedPubMedCentralGoogle Scholar
  37. Maquet P (1997) Positron emission tomography studies of sleep and sleep disorders. J Neurol 244:S23–S28CrossRefPubMedGoogle Scholar
  38. McGinty D, Szymusiak R (2011) Neural control of sleep in mammals. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. Elsevier/Saunders, Philadelphia, pp 76–91CrossRefGoogle Scholar
  39. Mignot E, Nishino S, Guilleminault C, Dement WC (1994) Modafinil binds to the dopamine uptake carrier site with low affinity. Sleep 17:436–437CrossRefPubMedGoogle Scholar
  40. Miller JD, Farber J, Gatz P, Roffwarg H, German DC (1983) Activity of mesencephalic dopamine and non-dopamine neurons across stages of sleep and walking in the rat. Brain Res 273:133–141CrossRefPubMedGoogle Scholar
  41. Murillo-Rodriguez E, Haro R, Palomero-Rivero M, Millan-Aldaco D, Drucker-Colin R (2007) Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats. Behav Brain Res 176:353–357CrossRefPubMedGoogle Scholar
  42. Oishi Y, Lazarus M (2017) The control of sleep and wakefulness by mesolimbic dopamine systems. Neurosci Res 118:66–73CrossRefPubMedGoogle Scholar
  43. Oishi Y, Suzuki Y, Takahashi K, Yonezawa T, Kanda T, Takata Y, Cherasse Y, Lazarus M (2017) Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D2-like receptors in mice. Brain Struct Funct 222:2907–2915CrossRefPubMedGoogle Scholar
  44. Qiu MH, Liu W, Qu WM, Urade Y, Lu J, Huang ZL (2012) The role of nucleus accumbens core/shell in sleep-wake regulation and their involvement in modafinil-induced arousal. PLoS One 7:e45471ADSCrossRefPubMedPubMedCentralGoogle Scholar
  45. Qu WM, Huang ZL, Xu XH, Matsumoto N, Urade Y (2008) Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. J Neurosci 28:8462–8469CrossRefPubMedGoogle Scholar
  46. Qu WM, Xu XH, Yan MM, Wang YQ, Urade Y, Huang ZL (2010) Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice. J Neurosci 30:4382–4389CrossRefPubMedGoogle Scholar
  47. Retey JV, Adam M, Khatami R, Luhmann UF, Jung HH, Berger W, Landolt HP (2007) A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clin Pharmacol Ther 81:692–698CrossRefPubMedGoogle Scholar
  48. Rupp TL, Wesensten NJ, Newman R, Balkin TJ (2013) PER3 and ADORA2A polymorphisms impact neurobehavioral performance during sleep restriction. J Sleep Res 22:160–165CrossRefPubMedGoogle Scholar
  49. Sanders-Bush E, Hazelwood L (2011) 5-Hydroxytryptamine (serotonin) and dopamine. In: Brunton LL, Chabner BA, Knollmann BC (eds) Goodman and Gilman’s: the pharmacological basis of therapeutics. McGraw-Hill, New YorkGoogle Scholar
  50. Schmitt KC, Reith ME (2011) The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. PLoS One 6:e25790ADSCrossRefPubMedPubMedCentralGoogle Scholar
  51. Shouse MN, Staba RJ, Saquib SF, Farber PR (2000) Monoamines and sleep: microdialysis findings in pons and amygdala. Brain Res 860:181–189CrossRefPubMedGoogle Scholar
  52. Siegel JM (2011) REM sleep. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. Elsevier/Saunders, Philadelphia, pp 92–111CrossRefGoogle Scholar
  53. Steinfels GF, Heym J, Strecker RE, Jacobs BL (1983) Behavioral correlates of dopaminergic unit activity in freely moving cats. Brain Res 258:217–228CrossRefPubMedGoogle Scholar
  54. Taylor NE, Van Dort CJ, Kenny JD, Pei J, Guidera JA, Vlasov KY, Lee JT, Boyden ES, Brown EN, Solt K (2016) Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia. Proc Natl Acad Sci U S AGoogle Scholar
  55. Tellez LA, Perez IO, Simon SA, Gutierrez R (2012) Transitions between sleep and feeding states in rat ventral striatum neurons. J Neurophysiol 108:1739–1751CrossRefPubMedPubMedCentralGoogle Scholar
  56. Trulson ME, Preussler DW (1984) Dopamine-containing ventral tegmental area neurons in freely moving cats: activity during the sleep-waking cycle and effects of stress. Exp Neurol 83:367–377CrossRefPubMedGoogle Scholar
  57. Urbano FJ, Leznik E, Llinas RR (2007) Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling. Proc Natl Acad Sci U S A 104:12554–12559ADSCrossRefPubMedPubMedCentralGoogle Scholar
  58. Van Dongen HP, Hinson JM, Whitney P, Satterfield BC, Schmidt MA, Wisor JP (2017) Feedback blunting due to sleep deprivation is affected by dopaminergic genotype. In: Cognitive Neuroscience Society, annual meetingGoogle Scholar
  59. Venkatraman V, Chuah YM, Huettel SA, Chee MW (2007) Sleep deprivation elevates expectation of gains and attenuates response to losses following risky decisions. Sleep 30:603–609CrossRefPubMedGoogle Scholar
  60. Venkatraman V, Huettel SA, Chuah LY, Payne JW, Chee MW (2011) Sleep deprivation biases the neural mechanisms underlying economic preferences. J Neurosci 31:3712–3718CrossRefPubMedGoogle Scholar
  61. Volkow ND, Tomasi D, Wang GJ, Telang F, Fowler JS, Logan J, Benveniste H, Kim R, Thanos PK, Ferre S (2012) Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain. J Neurosci 32:6711–6717CrossRefPubMedPubMedCentralGoogle Scholar
  62. Whitney P, Hinson JM, Jackson ML, Van Dongen HP (2015) Feedback blunting: total sleep deprivation impairs decision making that requires updating based on feedback. Sleep 38:745–754CrossRefPubMedPubMedCentralGoogle Scholar
  63. Wisor J (2013) Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions. Front Neurol 4:139CrossRefPubMedPubMedCentralGoogle Scholar
  64. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001) Dopaminergic role in stimulant-induced wakefulness. J Neurosci 21:1787–1794PubMedGoogle Scholar
  65. Xiao C, Cho JR, Zhou C, Treweek JB, Chan K, McKinney SL, Yang B, Gradinaru V (2016) Cholinergic mesopontine signals govern locomotion and reward through dissociable midbrain pathways. Neuron 90:333–347CrossRefPubMedPubMedCentralGoogle Scholar
  66. Zhang JP, Xu Q, Yuan XS, Cherasse Y, Schiffmann SN, de Kerchove d’Exaerde A, Qu WM, Urade Y, Lazarus M, Huang ZL, Li RX (2013) Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation. Front Neuroanat 7:43CrossRefPubMedPubMedCentralGoogle Scholar
  67. Zhu X, Ottenheimer D, DiLeone RJ (2016) Activity of D1/2 receptor expressing neurons in the nucleus accumbens regulates running, locomotion, and food intake. Front Behav Neurosci 10:66CrossRefPubMedPubMedCentralGoogle Scholar
  68. Zolkowska D, Jain R, Rothman RB, Partilla JS, Roth BL, Setola V, Prisinzano TE, Baumann MH (2009) Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil. J Pharmacol Exp Ther 329:738–746CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Biomedical SciencesElson S. Floyd College of Medicine, Washington State UniversitySpokaneUSA

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