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Neurochemical Research

, Volume 38, Issue 8, pp 1616–1623 | Cite as

Microinjection of Adenosine into the Hypothalamic Ventrolateral Preoptic Area Enhances Wakefulness via the A1 Receptor in Rats

  • Jin Zhang
  • Dou Yin
  • Fang Wu
  • Gongliang Zhang
  • Chuanwei Jiang
  • Zhen Li
  • Liecheng WangEmail author
  • Kai WangEmail author
Original Paper

Abstract

Adenosine (AD) is a nucleic acid component that is critical for energy metabolism in the body. AD modulates numerous neural functions in the central nervous system, including the sleep-wake cycle. Previous studies have indicated that the A1 receptor (A1R) or A2A receptor (A2AR) may mediate the effects of AD on the sleep-wake cycle. The hypothalamic ventrolateral preoptic area (VLPO) initiates and maintains normal sleep. Histological studies have shown A1R are widely expressed in brain tissue, whereas A2AR expression is limited in the brain and undetectable in the VLPO. We hypothesize therefore, that AD modulates the sleep-wake cycle through A1R in the VLPO. In the present study, bilateral microinjection of AD or an AD transporter inhibitor (s-(4-nitrobenzyl)-6-thioinosine) into the VLPO of rats decreased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. An A1R agonist (N6-cyclohexyladenosine) produced similar effects in the VLPO. Microinjection of an A1R antagonist (8-cyclopentyl-1,3-dimethylxanthine) into the VLPO enhanced NREM sleep and diminished AD-induced wakefulness. These data indicate that AD enhances wakefulness in the VLPO via A1R in rats.

Keywords

Adenosine Ventrolateral preoptic area Sleep Rat 

Notes

Acknowledgments

This research was supported by the National Natural Science Foundation of China (81071075 and 81271217), Doctoral Program Foundation of Institutions of Higher Education of China (20093420120004) and Plan for National Science Fund for Distinguished Young Scholars of Anhui Medical University (GJJQ-0801).

References

  1. 1.
    Feldberg W, Sherwood SL (1954) Injections of drugs into the lateral ventricle of the cat. J Physiol 123:148–167PubMedGoogle Scholar
  2. 2.
    Radulovacki M, Virus RM, Djuricic-Nedelson M, Green RD (1984) Adenosine analogs and sleep in rats. J Pharmacol Exp Ther 228:268–274PubMedGoogle Scholar
  3. 3.
    Schwierin B, Borbély AA, Tobler I (1996) Effects of N6-cyclopentyladenosine and caffeine on sleep regulation in the rat. Eur J Pharmacol 300:163–171PubMedCrossRefGoogle Scholar
  4. 4.
    Portas CM, Thakkar M, Rainnie DG, Greene RW, McCarley RW (1997) Role of adenosine in behavioral state modulation: a microdialysis study in the freely moving cat. Neuroscience 79:225–235PubMedCrossRefGoogle Scholar
  5. 5.
    Yanik G, Glaum S, Radulovacki M (1987) The dose-response effects of caffeine on sleep in rats. Brain Res 403:177–180PubMedCrossRefGoogle Scholar
  6. 6.
    Huston JP, Haas HL, Boix F, Pfister M, Decking U, Schrader J, Schwarting RK (1996) Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats. Neuroscience 73:99–107PubMedCrossRefGoogle Scholar
  7. 7.
    Porkka-Heiskanen T, Strecker RE, McCarley RW (2000) Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience 99:507–517PubMedCrossRefGoogle Scholar
  8. 8.
    Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW (1997) Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276:1265–1268PubMedCrossRefGoogle Scholar
  9. 9.
    Satoh S, Matsumura H, Koike N, Tokunaga Y, Maeda T, Hayaishi O (1999) Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist. Eur J Neurosci 11:1587–1597PubMedCrossRefGoogle Scholar
  10. 10.
    Mendelson WB (2000) Sleep-inducing effects of adenosine microinjections into the medial preoptic area are blocked by flumazenil. Brain Res 852:479–481PubMedCrossRefGoogle Scholar
  11. 11.
    Noor-Alam M, Kumar S, Rai S, Methippara M, Szymusiak R, Mcginty D (2009) Role of adenosine A1 receptor in the perifornical-lateral hypothalamic area in sleep-wake regulation in rats. Brain Res 1304:96–104CrossRefGoogle Scholar
  12. 12.
    Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53:527–552PubMedGoogle Scholar
  13. 13.
    Thakkar MM, Engemann SC, Walsh KM, Sahota PK (2008) Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. Neuroscience 153:875–880PubMedCrossRefGoogle Scholar
  14. 14.
    Elmenhorst D, Meyer PT, Winz OH, Matusch A, Ermert J, Coenen HH, Basheer R, Haas HL, Zilles K, Bauer A (2007) Sleep deprivation increases A1 adenosine receptor binding in the human brain: a positron emission tomography study. J Neurosci 27:2410–2415PubMedCrossRefGoogle Scholar
  15. 15.
    Coleman CG, Baghdoyan HA, Lydic R (2006) Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6 J mouse increases pontine acetylcholine release and sleep. J Neurochem 96:1750–1759PubMedCrossRefGoogle Scholar
  16. 16.
    Satoh S, Matsumura H, Suzuki F, Hayaishi O (1996) Promotion of sleep mediated by the A2a-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D2 in rats. Proc Natl Acad Sci USA 93:5980–5984PubMedCrossRefGoogle Scholar
  17. 17.
    Methippara MM, Kumar S, Alam MN, Szymusiak R, McGinty D (2005) Effects on sleep of microdialysis of adenosine A1 and A2a receptor analogs into the lateral preoptic area of rats. Am J Physiol Regul Integr Comp Physiol 289:R1715–R1723PubMedCrossRefGoogle Scholar
  18. 18.
    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 8:858–859PubMedCrossRefGoogle Scholar
  19. 19.
    Lu J, Greco MA, Shiromani P, Saper CB (2000) Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep. J Neurosci 20:3830–3842PubMedGoogle Scholar
  20. 20.
    Sherin JE, Shiromani PJ, McCarley RW, Saper CB (1996) Activation of ventrolateral preoptic neurons during sleep. Science 271:216–219PubMedCrossRefGoogle Scholar
  21. 21.
    Gong H, Szymusiak R, King J, Steininger T, McGinty D (2000) Sleep-related c-Fos protein expression in the preoptic hypothalamus: effects of ambient warming. Am J Physiol Regul Integr Comp Physiol 279:R2079–R2088PubMedGoogle Scholar
  22. 22.
    Szymusiak R, Alam N, Steininger TL, McGinty D (1998) Sleep-waking discharge patterns of ventrolateral preoptic/anterior hypothalamic neurons in rats. Brain Res 803:178–188PubMedCrossRefGoogle Scholar
  23. 23.
    Gong H, McGinty D, Guzman-Marin R, Chew KT, Stewart D, Szymusiak R (2004) Activation of c-fos in GABAergic neurones in the preoptic area during sleep and in response to sleep deprivation. J Physiol 556:935–946PubMedCrossRefGoogle Scholar
  24. 24.
    Sherin JE, Elmquist JK, Torrealba F, Saper CB (1998) Innervation of histaminergic tuberomammillary neurons by GABAergic and galaninergic neurons in the ventrolateral preoptic nucleus of the rat. J Neurosci 18:4705–4721PubMedGoogle Scholar
  25. 25.
    Steininger TL, Gong H, McGinty D, Szymusiak R (2001) Subregional organization of preoptic area/anterior hypothalamic projections to arousal-related monoaminergic cell groups. J Comp Neurol 429:638–653PubMedCrossRefGoogle Scholar
  26. 26.
    Yoshida K, McCormack S, España RA, Crocker A, Scammell TE (2006) Afferents to the orexin neurons of the rat brain. J Comp Neurol 494:845–861PubMedCrossRefGoogle Scholar
  27. 27.
    Yaar R, Jones MR, Chen JF, Ravid K (2005) Animal models for the study of adenosine receptor function. J Cell Physiol 202:9–20PubMedCrossRefGoogle Scholar
  28. 28.
    Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:1461–1468PubMedCrossRefGoogle Scholar
  29. 29.
    Reppert SM, Weaver DR, Stehle JH, Rivkees SA (1991) Molecular cloning and characterization of a rat A1-adenosine receptor that is widely expressed in brain and spinal cord. Mol Endocrinol 5:1037–1048PubMedCrossRefGoogle Scholar
  30. 30.
    Rivkees SA, Price SL, Zhou FC (1995) Immunohistochemical detection of A1 adenosine receptors in rat brain with emphasis on localization in the hippocampal formation, cerebral cortex, cerebellum, and basal ganglia. Brain Res 677:193–203PubMedCrossRefGoogle Scholar
  31. 31.
    Rosin DL, Robeva A, Woodard RL, Guyenet PG, Linden J (1998) Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system. J Comp Neurol 401:163–186PubMedCrossRefGoogle Scholar
  32. 32.
    Huang ZL, Urade Y, Hayaishi O (2011) The role of adenosine in the regulation of sleep. Curr Top Med Chem 11:1047–1057PubMedCrossRefGoogle Scholar
  33. 33.
    Zhang G, Wang L, Liu H, Zhang J (2004) Substance P promotes sleep in the ventrolateral preoptic area of rats. Brain Res 1028:225–232PubMedCrossRefGoogle Scholar
  34. 34.
    Paxins G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic Press, San DiegoGoogle Scholar
  35. 35.
    Virus RM, Ticho S, Pilditch M, Radulovacki M (1990) A comparison of the effects of caffeine, 8-cyclopentyltheophylline, and alloxazine on sleep in rats. Possible roles of central nervous system adenosine receptors. Neuropsychopharmacology 3:243–249PubMedGoogle Scholar
  36. 36.
    Marks GA, Shaffery JP, Speciale SG, Birabil CG (2003) Enhancement of rapid eye movement sleep in the rat by actions at A1 and A2a adenosine receptor subtypes with a differential sensitivity to atropine. Neuroscience 116:913–920PubMedCrossRefGoogle Scholar
  37. 37.
    Strecker RE, Morairty SR, Thakkar MM, Porkka-Heiskanen T, Basheer R, Dauphin LJ, Rainnie DG, Greene RW, McCarley RW (2000) Adenosinergic modulation of basal forebrain andpreoptic/anterior hypothalamic neuronal activity in the control of behavioral state. Behav Brain Res 115:183–204PubMedCrossRefGoogle Scholar
  38. 38.
    Thakkar MM, Delgiacco RA, Strecker RE, McCarley RW (2003) Adenosinergic inhibition of basal forebrain wakefulness-active neurons: a simultaneous unit recording and microdialysis study in freely behaving cats. Neuroscience 122:1107–1113PubMedCrossRefGoogle Scholar
  39. 39.
    Urade Y, Eguchi N, Qu WM, Sakata M, Huang ZL, Chen JF, Schwarzschild MA, Fink JS, Hayaishi O (2003) Sleep regulation in adenosine A2A receptor-deficient mice. Neurology 61:S94–S96PubMedCrossRefGoogle Scholar
  40. 40.
    Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492PubMedGoogle Scholar
  41. 41.
    Obrietan K, Belousov AB, Heller HC, van den Pol AN (1995) Adenosine pre- and postsynaptic modulation of glutamate-dependent calcium activity in hypothalamic neurons. J Neurophysiol 74:2150–2162PubMedGoogle Scholar
  42. 42.
    Morairty S, Rainnie D, McCarley R, Greene R (2004) Disinhibition of ventrolateral preoptic area sleep-active neurons by adenosine: a new mechanism for sleep promotion. Neuroscience 123:451–457PubMedCrossRefGoogle Scholar
  43. 43.
    Chamberlin NL, Arrigoni E, Chou TC, Scammell TE, Greene RW, Saper CB (2003) Effects of adenosine on gabaergic synaptic inputs to identified ventrolateral preoptic neurons. Neuroscience 119:913–918PubMedCrossRefGoogle Scholar
  44. 44.
    Gallopin T, Luppi PH, Cauli B, Urade Y, Rossier J, Hayaishi O, Lambolez B, Fort P (2005) The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus. Neuroscience 134:1377–1390PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jin Zhang
    • 1
    • 2
  • Dou Yin
    • 2
  • Fang Wu
    • 2
  • Gongliang Zhang
    • 2
  • Chuanwei Jiang
    • 3
  • Zhen Li
    • 2
  • Liecheng Wang
    • 2
    Email author
  • Kai Wang
    • 1
    Email author
  1. 1.Department of NeurologyThe First Hospital of Anhui Medical UniversityHefeiPeople’s Republic of China
  2. 2.Department of Physiology, School of Basic Medical ScienceAnhui Medical UniversityHefeiPeople’s Republic of China
  3. 3.Department of Physiology, College of Traditional Chinese MedicineAnhui Medical UniversityHefeiPeople’s Republic of China

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