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Novel Role for Adenosine in Circadian Rhythms and Alcohol Use Disorders

Christina L Ruby, Marc L Purazo, David J Bunion, Kaitlyn L Palmer

Abstract


In the central nervous system, the nucleoside adenosine regulates neuronal activity by modulating the actions of other neurotransmitter systems, thereby influencing many different physiological processes and behaviors.  Adenosinergic mechanisms are especially important in fine-tuning glutamatergic neurotransmission.  Astrocytic release of adenosine triphosphate and its subsequent extracellular breakdown provides adenosine to drive homeostatic sleep.  Acute ethanol (alcohol) exposure increases extracellular adenosine, which mediates the ataxic and hypnotic/sedative effects of alcohol, while chronic ethanol exposure leads to downregulated adenosine signaling that underlies insomnia, a major predictor of relapse.  Adenosine gates glutamatergic input to the circadian clock located in the suprachiasmatic nucleus of the hypothalamus, modulating both photic (light-induced) and nonphotic (behaviorally-induced) synchronization of circadian activity rhythms.    A recent study using mice lacking the equilibrative nucleoside transporter 1, a well-established animal model of alcohol addiction, suggests an expanded role for adenosine in cellular and behavioral circadian timing and alcohol intake, particularly during chronodisruption.

Keywords


adenosine; glutamate; circadian rhythms; sleep; alcohol; astrocytes; neuroglial interactions

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References


Abe, H., Rusak, B., & Robertson, H. A. (1991). Photic Induction of Fos Protein in the Suprachiasmatic Nucleus Is Inhibited by the NMDA Receptor Antagonist MK-801. Neurosci Lett 127(1): 9-12. doi: 10.1016/0304-3940(91)90881-S

Alanko, L., Stenberg, D., & Porkka-Heiskanen, T. (2003). Nitrobenzylthioinosine (NBMPR) binding and nucleoside transporter ENT1 mRNA expression after prolonged wakefulness and recovery sleep in the cortex and basal forebrain of rat. J Sleep Res 12(4): 299-304.

Albrecht, U., Zheng, B., Larkin, D., Sun, Z. S., & Lee, C. C. (2001). mPer1 and mPer2 are essential for normal resetting of the circadian clock. J Biol Rhythms 16(2): 100-104.

Allen, R. P., Wagman, A., Faillace, L. A., & McIntosh, M. (1971). Electroencephalographic (EEG) sleep recovery following prolonged alcohol intoxication in alcoholics. J Nerv Ment Dis 153(6): 424-433.

Antle, M. C., Steen, N. M., & Mistlberger, R. E. (2001). Adenosine and caffeine modulate circadian rhythms in the Syrian hamster. Neuroreport 12(13): 2901-2905.

Aoyama, S., Kase, H., & Borrelli, E. (2000). Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an adenosine A2A receptor antagonist. J Neurosci 20(15): 5848-5852.

Araque, A., Parpura, V., Sanzgiri, R. P., & Haydon, P. G. (1999). Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 22(5): 208-215.

Arolfo, M. P., Yao, L., Gordon, A. S., Diamond, I., & Janak, P. H. (2004). Ethanol operant self-administration in rats is regulated by adenosine A2 receptors. Alcohol Clin Exp Res 28(9): 1308-1316.

Asatryan, L., Nam, H. W., Lee, M. R., Thakkar, M. M., Saeed Dar, M., Davies, D. L., & Choi, D. S. (2011). Implication of the purinergic system in alcohol use disorders. Alcohol Clin Exp Res 35(4): 584-594.

Bachmann, V., Klaus, F., Bodenmann, S., Schafer, N., Brugger, P., Huber, S., . . . Landolt, H. P. (2012). Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans. Cereb Cortex 22(4): 962-970. doi: 10.1093/cercor/bhr173

Basheer, R., Strecker, R. E., Thakkar, M. M., & McCarley, R. W. (2004). Adenosine and sleep-wake regulation. Prog Neurobiol 73(6): 379-396. doi: 10.1016/j.pneurobio.2004.06.004

Blutstein, T., & Haydon, P. G. (2013). The importance of astrocyte-derived purines in the modulation of sleep. Glia 61(2): 129-139. doi: 10.1002/glia.22422

Brower, K. J. (2001). Alcohol's effects on sleep in alcoholics. Alcohol Res Health, 25(2), 110-125.

Brower, K. J., Aldrich, M. S., & Hall, J. M. (1998). Polysomnographic and subjective sleep predictors of alcoholic relapse. Alcohol Clin Exp Res 22(8): 1864-1871.

Brower, K. J., & Perron, B. E. (2010). Sleep disturbance as a universal risk factor for relapse in addictions to psychoactive substances. Med Hypotheses 74(5): 928-933.

Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012). Control of Sleep and Wakefulness. Physiol Rev 92(3): 1087-1187. doi: 10.1152/physrev.00032.2011

Burnstock, G. (2006). Historical review: ATP as a neurotransmitter. Trends Pharmacol Sci 27(3): 166-176. doi: 10.1016/j.tips.2006.01.005

Burnstock, G. (2008). Purinergic signalling and disorders of the central nervous system. Nat Rev Drug Discov 7(7): 575-590. doi: 10.1038/nrd2605

Chen, J., Nam, H. W., Lee, M. R., Hinton, D. J., Choi, S., Kim, T., . . . Choi, D. S. (2010). Altered glutamatergic neurotransmission in the striatum regulates ethanol sensitivity and intake in mice lacking ENT1. Behav Brain Res 208(2): 636-642. doi: 10.1016/j.bbr.2010.01.011

Choi, D. S., Cascini, M. G., Mailliard, W., Young, H., Paredes, P., McMahon, T., . . . Messing, R. O. (2004). The type 1 equilibrative nucleoside transporter regulates ethanol intoxication and preference. Nat Neurosci 7(8): 855-861.

Ciruela, F., Casado, V., Rodrigues, R. J., Lujan, R., Burgueno, J., Canals, M., . . . Franco, R. (2006). Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci 26(7): 2080-2087. doi: 10.1523/JNEUROSCI.3574-05.2006

Colrain, I. M., Crowley, K. E., Nicholas, C. L., Padilla, M., & Baker, F. C. (2009). The impact of alcoholism on sleep evoked Delta frequency responses. Biol Psychiatry 66(2): 177-184. doi: 10.1016/j.biopsych.2008.10.010

Colwell, C. S., Foster, R. G., & Menaker, M. (1991). NMDA Receptor Antagonists Block the Effects of Light on Circadian Behavior in the Mouse. Brain Res 554(1-2): 105-110. doi: 10.1016/0006-8993(91)90177-W

Cunha, R. A., Ferre, S., Vaugeois, J. M., & Chen, J. F. (2008). Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders. Curr Pharm Des 14(15): 1512-1524.

Dias, R. B., Rombo, D. M., Ribeiro, J. A., Henley, J. M., & Sebastiao, A. M. (2013). Adenosine: setting the stage for plasticity. Trends Neurosci 36(4): 248-257. doi: 10.1016/j.tins.2012.12.003

Dibner, C., Schibler, U., & Albrecht, U. (2010). The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 72: 517-549. doi: 10.1146/annurev-physiol-021909-135821

Ding, J. M., Chen, D., Weber, E. T., Faiman, L. E., Rea, M. A., & Gillette, M. U. (1994). Resetting the Biological Clock - Mediation of Nocturnal Circadian Shifts by Glutamate and NO. Science 266(5191): 1713-1717. doi: DOI 10.1126/science.7527589

Diogenes, M. J., Neves-Tome, R., Fucile, S., Martinello, K., Scianni, M., Theofilas, P., . . . Sebastiao, A. M. (2014). Homeostatic control of synaptic activity by endogenous adenosine is mediated by adenosine kinase. Cereb Cortex 24(1): 67-80. doi: 10.1093/cercor/bhs284

Dunwiddie, T. V., & Masino, S. A. (2001). The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24: 31-55.

Ehlers, C. L., & Slawecki, C. J. (2000). Effects of chronic ethanol exposure on sleep in rats. Alcohol 20(2): 173-179.

El Yacoubi, M., Ledent, C., Menard, J. F., Parmentier, M., Costentin, J., & Vaugeois, J. M. (2000). The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A(2A) receptors. Br J Pharmacol 129(7): 1465-1473.

Ferre, S., Woods, A. S., Navarro, G., Aymerich, M., Lluis, C., & Franco, R. (2010). Calcium-mediated modulation of the quaternary structure and function of adenosine A2A-dopamine D2 receptor heteromers. Curr Opin Pharmacol 10(1): 67-72. doi: 10.1016/j.coph.2009.10.002

Frank, M. G. (2013). Astroglial regulation of sleep homeostasis. Curr Opin Neurobiol 23(5): 812-818. doi: 10.1016/j.conb.2013.02.009

Fredholm, B. B. (2010). Adenosine receptors as drug targets. Exp Cell Res 316(8): 1284-1288. doi: 10.1016/j.yexcr.2010.02.004

Gass, N., Ollila, H. M., Utge, S., Partonen, T., Kronholm, E., Pirkola, S., . . . Paunio, T. (2010). Contribution of adenosine related genes to the risk of depression with disturbed sleep. J Affect Disord 126(1-2): 134-139.

Halassa, M. M., Fellin, T., & Haydon, P. G. (2009). Tripartite synapses: roles for astrocytic purines in the control of synaptic physiology and behavior. Neuropharmacology 57(4): 343-346. doi: 10.1016/j.neuropharm.2009.06.031

Halassa, M. M., Florian, C., Fellin, T., Munoz, J. R., Lee, S. Y., Abel, T., . . . Frank, M. G. (2009). Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61(2): 213-219.

Hallworth, R., Cato, M., Colbert, C., & Rea, M. A. (2002). Presynaptic adenosine A1 receptors regulate retinohypothalamic neurotransmission in the hamster suprachiasmatic nucleus. J Neurobiol 52(3): 230-240.

Hamilton, N. B., & Attwell, D. (2010). Do astrocytes really exocytose neurotransmitters? Nat Rev Neurosci 11(4): 227-238. doi: 10.1038/nrn2803

Harvey, J., & Lacey, M. G. (1997). A postsynaptic interaction between dopamine D1 and NMDA receptors promotes presynaptic inhibition in the rat nucleus accumbens via adenosine release. J Neurosci 17(14): 5271-5280.

Hodgkinson, C. A., Yuan, Q., Xu, K., Shen, P. H., Heinz, E., Lobos, E. A., . . . Goldman, D. (2008). Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol 43(5): 505-515. doi: 10.1093/alcalc/agn032

Houchi, H., Persyn, W., Legastelois, R., & Naassila, M. (2013). The adenosine A2A receptor agonist CGS 21680 decreases ethanol self-administration in both non-dependent and dependent animals. Addict Biol 18(5): 812-825. doi: 10.1111/adb.12032

Kaplan, G. B., Bharmal, N. H., Leite-Morris, K. A., & Adams, W. R. (1999). Role of adenosine A1 and A2A receptors in the alcohol withdrawal syndrome. Alcohol 19(2): 157-162.

Kim, J. H., Karpyak, V. M., Biernacka, J. M., Nam, H. W., Lee, M. R., Preuss, U. W., . . . Choi, D. S. (2011). Functional role of the polymorphic 647 T/C variant of ENT1 (SLC29A1) and its association with alcohol withdrawal seizures. PLoS One 6(1): e16331.

Kubota, T., De, A., Brown, R. A., Simasko, S. M., & Krueger, J. M. (2002). Diurnal effects of acute and chronic administration of ethanol on sleep in rats. Alcohol Clin Exp Res 26(8): 1153-1161. doi: 10.1097/01.ALC.0000024292.05785.03

Latini, S., & Pedata, F. (2001). Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J Neurochem 79(3): 463-484.

Lazarus, M., Shen, H. Y., Cherasse, Y., Qu, W. M., Huang, Z. L., Bass, C. E., . . . Chen, J. F. (2011). Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 31(27): 10067-10075.

Lovatt, D., Xu, Q., Liu, W., Takano, T., Smith, N. A., Schnermann, J., . . . Nedergaard, M. (2012). Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity. Proc Natl Acad Sci U S A 109(16): 6265-6270. doi: 10.1073/pnas.1120997109

Marpegan, L., Swanstrom, A. E., Chung, K., Simon, T., Haydon, P. G., Khan, S. K., . . . Beaule, C. (2011). Circadian regulation of ATP release in astrocytes. J Neurosci 31(23): 8342-8350.

Mendelson, W. B., Majchrowicz, E., Mirmirani, N., Dawson, S., Gillin, J. C., & Wyatt, R. J. (1978). Sleep during chronic ethanol administration and withdrawal in rats. J Stud Alcohol 39(7): 1213-1223.

Mintz, E. M., & Albers, H. E. (1997). Microinjection of NMDA into the SCN region mimics the phase shifting effect of light in hamsters. Brain Res, 758(1-2), 245-249.

Mintz, E. M., Marvel, C. L., Gillespie, C. F., Price, K. M., & Albers, H. E. (1999). Activation of NMDA receptors in the suprachiasmatic nucleus produces light-like phase shifts of the circadian clock in vivo. J Neurosci 19(12): 5124-5130.

Moore, R. Y. (1983). Organization and Function of a Central Nervous-System Circadian Oscillator - the Suprachiasmatic Hypothalamic Nucleus. Fed Proc 42(11): 2783-2789.

Mukherjee, S., Kazerooni, M., & Simasko, S. M. (2008). Dose-response study of chronic alcohol induced changes in sleep patterns in rats. Brain Res 1208: 120-127. doi: 10.1016/j.brainres.2008.02.079

Mukherjee, S., & Simasko, S. M. (2009). Chronic alcohol treatment in rats alters sleep by fragmenting periods of vigilance cycling in the light period with extended wakenings. Behav Brain Res 198(1): 113-124. doi: 10.1016/j.bbr.2008.10.026

Murillo-Rodriguez, E., Blanco-Centurion, C., Gerashchenko, D., Salin-Pascual, R. J., & Shiromani, P. J. (2004). The diurnal rhythm of adenosine levels in the basal forebrain of young and old rats. Neuroscience 123(2): 361-370.

Naassila, M., Ledent, C., & Daoust, M. (2002). Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors. J Neurosci 22(23): 10487-10493.

Nagy, L. E., Diamond, I., Casso, D. J., Franklin, C., & Gordon, A. S. (1990). Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter. J Biol Chem 265(4): 1946-1951.

Nam, H. W., Lee, M. R., Hinton, D. J., & Choi, D. S. (2010). Reduced effect of NMDA glutamate receptor antagonist on ethanol-induced ataxia and striatal glutamate levels in mice lacking ENT1. Neurosci Lett 479(3): 277-281. doi: 10.1016/j.neulet.2010.05.079

Nam, H. W., Lee, M. R., Zhu, Y., Wu, J., Hinton, D. J., Choi, S., . . . Choi, D. S. (2011). Type 1 equilibrative nucleoside transporter regulates ethanol drinking through accumbal N-methyl-D-aspartate receptor signaling. Biol Psychiatry 69(11): 1043-1051.

Oike, H., Kobori, M., Suzuki, T., & Ishida, N. (2011). Caffeine lengthens circadian rhythms in mice. Biochem Biophys Res Commun 410(3): 654-658.

Parkinson, F. E., Ferguson, J., Zamzow, C. R., & Xiong, W. (2006). Gene expression for enzymes and transporters involved in regulating adenosine and inosine levels in rat forebrain neurons, astrocytes and C6 glioma cells. J Neurosci Res 84(4): 801-808. doi: 10.1002/jnr.20988

Parkinson, F. E., Xiong, W., & Zamzow, C. R. (2005). Astrocytes and neurons: different roles in regulating adenosine levels. Neurol Res 27(2): 153-160.

Parkinson, F. E., Xiong, W., Zamzow, C. R., Chestley, T., Mizuno, T., & Duckworth, M. L. (2009). Transgenic expression of human equilibrative nucleoside transporter 1 in mouse neurons. J Neurochem 109(2): 562-572.

Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J. Y., . . . Haydon, P. G. (2005). Astrocytic purinergic signaling coordinates synaptic networks. Science 310(5745): 113-116. doi: 10.1126/science.1116916

Pickard, G. E. (1982). The Afferent Connections of the Suprachiasmatic Nucleus of the Golden-Hamster with Emphasis on the Retinohypothalamic Projection. J Comp Neurol 211(1): 65-83. doi: DOI 10.1002/cne.902110107

Porkka-Heiskanen, T., Strecker, R. E., Thakkar, M., Bjorkum, A. A., Greene, R. W., & McCarley, R. W. (1997). Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness. Science 276(5316): 1265-1268. doi: DOI 10.1126/science.276.5316.1265

Radulovacki, M., Virus, R. M., Djuricicnedelson, M., & Green, R. D. (1984). Adenosine-Analogs and Sleep in Rats. J Pharmacol Exp Ther 228(2): 268-274.

Roehrs, T., & Roth, T. (2001). Sleep, sleepiness, and alcohol use. Alcohol Res Health 25(2): 101-109.

Ruby, C. L., Adams, C. A., Knight, E. J., Nam, H. W., & Choi, D. S. (2010). An essential role for adenosine signaling in alcohol abuse. Curr Drug Abuse Rev 3(3): 163-174.

Ruby, C. L., Brager, A. J., DePaul, M. A., Prosser, R. A., & Glass, J. D. (2009). Chronic ethanol attenuates circadian photic phase resetting and alters nocturnal activity patterns in the hamster. Am J Physiol Regul Integr Comp Physiol 297(3): R729-737.

Ruby, C. L., O'Connor, K. M., Ayers-Ringler, J., & Choi, D. S. (2014). Adenosine and glutamate in neuroglial interaction: implications for circadian disorders and alcoholism. Adv Neurobiol 11: 103-119. doi: 10.1007/978-3-319-08894-5_6

Ruby, C. L., Prosser, R. A., DePaul, M. A., Roberts, R. J., & Glass, J. D. (2009). Acute ethanol impairs photic and nonphotic circadian phase resetting in the Syrian hamster. Am J Physiol Regul Integr Comp Physiol 296(2): R411-418.

Ruby, C. L., Vadnie, C. A., Hinton, D. J., Abulseoud, O. A., Walker, D. L., O'Connor, K. M., . . . Choi, D. S. (2014). Adenosinergic regulation of striatal clock gene expression and ethanol intake during constant light. Neuropsychopharmacology 39(10): 2432-2440. doi: 10.1038/npp.2014.94

Schmitt, L. I., Sims, R. E., Dale, N., & Haydon, P. G. (2012). Wakefulness Affects Synaptic and Network Activity by Increasing Extracellular Astrocyte-Derived Adenosine. J Neurosci 32(13): 4417-4425. doi: 10.1523/Jneurosci.5689-11.2012

Seggio, J. A., Fixaris, M. C., Reed, J. D., Logan, R. W., & Rosenwasser, A. M. (2009). Chronic ethanol intake alters circadian phase shifting and free-running period in mice. J Biol Rhythms 24(4): 304-312.

Seggio, J. A., Logan, R. W., & Rosenwasser, A. M. (2007). Chronic ethanol intake modulates photic and non-photic circadian phase responses in the Syrian hamster. Pharmacol Biochem Behav 87(3): 297-305. doi: 10.1016/j.pbb.2007.05.001

Sharma, R., Engemann, S., Sahota, P., & Thakkar, M. M. (2010). Role of adenosine and wake-promoting basal forebrain in insomnia and associated sleep disruptions caused by ethanol dependence. J Neurochem 115(3): 782-794.

Short, J. L., Drago, J., & Lawrence, A. J. (2006). Comparison of ethanol preference and neurochemical measures of mesolimbic dopamine and adenosine systems across different strains of mice. Alcohol Clin Exp Res 30(4): 606-620.

Sigworth, L. A., & Rea, M. A. (2003). Adenosine A1 receptors regulate the response of the mouse circadian clock to light. Brain Res 960(1-2): 246-251.

Spanagel, R., Pendyala, G., Abarca, C., Zghoul, T., Sanchis-Segura, C., Magnone, M. C., . . . Albrecht, U. (2005). The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Nat Med 11(1): 35-42.

Thakkar, M. M., Delgiacco, R. A., Strecker, R. E., & McCarley, R. W. (2003). Adenosinergic inhibition of basal forebrain wakefulness-active neurons: a simultaneous unit recording and microdialysis study in freely behaving cats. Neuroscience 122(4): 1107-1113.

Thakkar, M. M., Engemann, S. C., Sharma, R., & Sahota, P. (2010). Role of wake-promoting basal forebrain and adenosinergic mechanisms in sleep-promoting effects of ethanol. Alcohol Clin Exp Res 34(6): 997-1005. doi: 10.1111/j.1530-0277.2010.01174.x

Veatch, L. M. (2006). Disruptions in sleep time and sleep architecture in a mouse model of repeated ethanol withdrawal. Alcohol Clin Exp Res 30(7): 1214-1222. doi: 10.1111/j.1530-0277.2006.00134.x

Verbanes, N. M., Zisk, C. F., Marinos, L. N., Dietzel, J. D., Maziarz, C. M., & Ruby, C. L. (2014). Caffeine potentiates circadian photic phase-resetting and delays light-entrained onset in mice. Soc Neurosci Abst #454.29.

Virus, R. M., Baglajewski, T., & Radulovacki, M. (1984). Circadian variation of [3H]N6-(L-phenylisopropyl)adenosine binding in rat brain. Neurosci Lett 46(2): 219-222.

Wall, M. J., & Dale, N. (2013). Neuronal transporter and astrocytic ATP exocytosis underlie activity-dependent adenosine release in the hippocampus. J Physiol 591(16): 3853-3871. doi: 10.1113/jphysiol.2013.253450




DOI: http://dx.doi.org/10.18103/mra.v2i6.395

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