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Adenosine A 1 and A 2A Receptors in Mouse Prefrontal Cortex Modulate Acetylcholine Release and Behavioral Arousal
Open accessAbstract
During prolonged intervals of wakefulness, brain adenosine levels rise within the basal forebrain and cortex. The view that adenosine promotes sleep is supported by the corollary that N -methylated xanthines such as caffeine increase brain and behavioral arousal by blocking adenosine receptors. The four subtypes of adenosine receptors are distributed heterogeneously throughout the brain, yet the neurotransmitter systems and brain regions through which adenosine receptor blockade causes arousal are incompletely understood. This study tested the hypothesis that adenosine A 1 and A 2A receptors in the prefrontal cortex contribute to the regulation of behavioral and cortical arousal. Dependent measures included acetylcholine (ACh) release in the prefrontal cortex, cortical electroencephalographic (EEG) power, and time to waking after anesthesia. Sleep and wakefulness were also quantified after microinjecting an adenosine A 1 receptor antagonist into the prefrontal cortex. The results showed that adenosine A 1 and A 2A receptors in the prefrontal cortex modulate cortical ACh release, behavioral arousal, EEG delta power, and sleep. Additional dual microdialysis studies revealed that ACh release in the pontine reticular formation is significantly altered by dialysis delivery of adenosine receptor agonists and antagonists to the prefrontal cortex. These data, and early brain transection studies demonstrating that the forebrain is not needed for sleep cycle generation, suggest that the prefrontal cortex modulates EEG and behavioral arousal via descending input to the pontine brainstem. The results provide novel evidence that adenosine A 1 receptors within the prefrontal cortex comprise part of a descending system that inhibits wakefulness.
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Direct wakefulness consolidation indirectly enhances subsequent SWS, and may thus facilitate the hypothesized mechanism for trazodone's benefits.
“In turn, direct wakefulness consolidation indirectly enhances subsequent SWS, and may thus facilitate the hypothesized mechanism for trazodone's benefits [27-29, 36]”
From Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers (2019) · cites this paper as [36]
The Results report that an adenosine A1 antagonist increased wakefulness and decreased NREM sleep in mice. The Discussion also reports increased slow-wave activity during NREM sleep in a sleep-deprivation context. Neither passage shows that consolidating wakefulness enhances subsequent slow-wave sleep or addresses trazodone’s benefits; no page numbers are available in our copy. (LLM, conf=0.73)
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Cites
Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624 · cited 3×
“(2005) study (5, 10, and 15 mg/kg) have been shown to induce locomotor activity (Fredholm et al., 1999; Lindskog et al., 2002).”
BackgroundAdenosine A2A, but not A1, receptors mediate the arousal effect of caffeine
Huang, Z.-L., Qu, W.-M., Eguchi, N., Chen, J.-F., Schwarzschild, M. A., Fredholm, B. B., Urade, Y., & Hayaishi, O. (2005) · Nature Neuroscience · doi:10.1038/nn1491 · Cited by 640
The prefrontal cortex in sleep
Muzur, A., Pace-Schott, E. F., & Hobson, J. A. (2002) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(02)01992-7 · Cited by 571
An essential role for orexins in emergence from general anesthesia
Kelz, M. B., Sun, Y., Chen, J., Cheng Meng, Q., Moore, J. T., Veasey, S. C., Dixon, S., Thornton, M., Funato, H., & Yanagisawa, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707146105 · Cited by 341
Flagged first, then by citations
Research works printed but not linked: 57
- 10.1016/S0893-133X(02)00290-7 · DOI
- Alaraj, 1998, Effects of caffeine on NMDA-evoked 45Ca2+ release in the rat dentate gyrus in vivo, Acta Neurobiol Exp (Wars), 58, 239, 10.55782/ane-1998-1278 · DOI
- 10.1016/0006-8993(84)90351-2 · DOI · Paper page
- 10.1097/00001756-200106130-00013 · DOI
- 10.1016/j.pneurobio.2004.06.004 · DOI
- Basheer, 2007, Sleep deprivation upregulates A1 adenosine receptors in the rat basal forebrain, Neuroreport, 18, 1895, 10.1097/WNR.0b013e3282f262f6 · DOI
- 10.1016/0006-8993(95)00590-M · DOI
- 10.1016/0014-4886(74)90079-X · DOI
- Carter, 1997, Hippocampal noradrenaline release in awake, freely moving rats is regulated by alpha-2 adrenoceptors but not by adenosine receptors, J Pharmacol Exp Ther, 281, 648, 10.1016/S0022-3565(24)36669-8 · DOI
- 10.1523/JNEUROSCI.0733-08.2008 · DOI
- 10.1111/j.1471-4159.2006.03700.x · DOI
- Crawley J (2000) Behavioral phenotyping of transgenic and knockout mice, What's wrong with my mouse? (Wiley-Liss, New York). · DOI
- 10.1021/jm00157a035 · DOI
- 10.1016/j.neuroscience.2003.08.045 · DOI
- Douglas, 2002, Prefrontal cortex acetylcholine release, EEG slow waves, and spindles are modulated by M2 autoreceptors in C57BL/6J mouse, J Neurophysiol, 87, 2817, 10.1152/jn.2002.87.6.2817 · DOI
- 10.1523/JNEUROSCI.5066-06.2007 · DOI
- 10.1016/S0896-6273(01)00285-9 · DOI
- 10.1016/S0306-4522(03)00031-9 · DOI
- 10.1016/j.brainresbull.2007.09.008 · DOI
- 10.1007/s00210-004-0970-1 · DOI
- 10.1117/1.1755233 · DOI
- 10.1016/0306-4522(96)00021-8 · DOI
- Jouvet, 1962, Research on the neural structures and responsible mechanisms in different phases of physiological sleep, Arch Ital Biol, 100, 125
- 10.1007/s002100000315 · DOI
- 10.1093/cercor/bhi079 · DOI · Paper page
- 10.1007/s002130051125 · DOI
- Leonard, 1997, Pontine nitric oxide modulates acetylcholine release, rapid eye movement sleep generation, and respiratory rate, J Neurosci, 17, 774, 10.1523/JNEUROSCI.17-02-00774.1997 · DOI
- Linden, 1999, Characterization of human A2B adenosine receptors: radioligand binding, western blotting, and coupling to G(q) in human embryonic kidney 293 cells and HMC-1 mast cells, Mol Pharmacol, 56, 705, 10.1016/S0026-895X(24)12531-X · DOI
- 10.1038/nature00817 · DOI
- 10.1016/S0014-2999(99)00659-7 · DOI
- 10.1038/sj.bjp.0705692 · DOI
- Lydic, 1993, Pedunculopontine stimulation alters respiration and increases ACh release in the pontine reticular formation, Am J Physiol, 264, R544
- 10.1016/S0306-4522(02)00561-4 · DOI
- 10.1046/j.0953-816x.2001.01619.x · DOI
- 10.1016/S0306-4522(00)00075-0 · DOI
- 10.1016/0013-4694(49)90066-8 · DOI
- 10.1016/0304-3940(96)12780-4 · DOI
- 10.1016/S0014-2999(96)00938-7 · DOI
- 10.1016/S0031-9384(97)00390-9 · DOI
- 10.1126/science.276.5316.1265 · DOI · Paper page
- 10.1016/S0306-4522(00)00220-7 · DOI
- 10.1053/smrv.2001.0201 · DOI
- 10.1179/016164105X21814 · DOI
- 10.1016/j.neuroscience.2007.06.057 · DOI
- Robert, 1998, Knockout mice: advantages and limitations for biological modeling. Definitions, principles and examples, Ann Dermatol Venereol, 125, 946
- Sonner, 1999, Mouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds, Anesth Analg, 89, 1030, 10.1213/00000539-199910000-00039 · DOI · Paper page
- Stenberg, 2003, Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor, J Sleep Res, 12, 283, 10.1046/j.0962-1105.2003.00367.x · DOI
- Steriade, 1990, Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems, J Neurosci, 10, 2541, 10.1523/JNEUROSCI.10-08-02541.1990 · DOI
- 10.1016/S0166-4328(00)00258-8 · DOI
- 10.1097/00000542-200304000-00018 · DOI
- 10.1097/00000542-200210000-00024 · DOI
- 10.1097/00000542-200506000-00015 · DOI
- 10.1159/000067831 · DOI
- Van Dongen, 2001, Caffeine eliminates psychomotor vigilance deficits from sleep inertia, Sleep, 24, 813, 10.1093/sleep/24.7.813 · DOI
- 10.1097/ALN.0b013e31818e3b1b · DOI
- Watson, 2006, In vivo measurements of neurotransmitters by microdialysis sampling, Anal Chem, 78, 1391, 10.1021/ac0693722 · DOI
- 10.1016/0006-8993(87)90046-1 · DOI
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Taylor, N. E., Van Dort, C. J., Kenny, J. D., Pei, J., Guidera, J. A., Vlasov, K. Y., Lee, J. T., Boyden, E. S., Brown, E. N., & Solt, K. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614340113 · Cited by 269
Self-citationAlcohol disrupts sleep homeostasis
Thakkar, M. M., Sharma, R., & Sahota, P. (2015) · Alcohol · doi:10.1016/j.alcohol.2014.07.019 · Cited by 262
Botton, P. H., Costa, M. S., Ardais, A. P., Mioranzza, S., Souza, D. O., da Rocha, J. B. T., & Porciúncula, L. O. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.05.034 · Cited by 140
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Leung, L. S., Luo, T., Ma, J., & Herrick, I. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.08.001 · Cited by 126
Caffeine and the Control of Cerebral Hemodynamics
Pelligrino, D. A., Xu, H.-L., & Vetri, F. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-091261 · Cited by 93
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La, A. L., Walsh, C. M., Neylan, T. C., Vossel, K. A., Yaffe, K., Krystal, A. D., Miller, B. L., & Karageorgiou, E. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-181145 · Cited by 83
Pal, D., Lipinski, W. J., Walker, A. J., Turner, A. M., & Mashour, G. A. (2011) · Anesthesiology · doi:10.1097/aln.0b013e318204e064 · Cited by 71
Comparison of (stereotactic) parcellations in mouse prefrontal cortex
Van De Werd, H. J. J. M., & Uylings, H. B. M. (2014) · Brain Structure and Function · doi:10.1007/s00429-013-0630-7 · Cited by 56
Sleep is more sensitive to high doses of caffeine in the middle years of life
Robillard, R., Bouchard, M., Cartier, A., Nicolau, L., & Carrier, J. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115575535 · Cited by 53
Metadata
- Authors
- Van Dort, C. J., Baghdoyan, H. A., & Lydic, R.
- Affiliations
- Pediatrics and Genetics (US)
- University of Michigan (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-01-21
- Volume
- 29
- Issue
- 3
- Pages
- 871-881
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3430130
- OpenAlex
- W2088462720
- Cited by
- 143
- References
- 4
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 5 · 2022: 11 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 10 · 2013: 6 · 2012: 16
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (MH45361)
- National Heart, Lung, and Blood Institute (R01HL057120, R01HL040881, R01HL065272)
- National Institute of Mental Health (R37MH045361, R01MH045361, MH-45361)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- adenosine A1 receptor, adenosine A2A receptor, prefrontal cortex, acetylcholine release, behavioral arousal, sleep regulation, wakefulness, EEG delta power, pontine reticular formation, adenosine receptor antagonists, caffeine
- MeSH terms
- Acetylcholine, Adenosine, Analysis of Variance, Animals, Arousal, Behavior, Animal, Caffeine, Chromatography, High Pressure Liquid, Electroencephalography, Electromyography, Male, Phenethylamines, Phosphodiesterase Inhibitors, Spectrum Analysis, Triazines, Triazoles, Xanthines, Prefrontal Cortex, Microdialysis, Receptor, Adenosine A1, Receptors, Adenosine A2, Mice, Adenosine A1 Receptor Antagonists, Adenosine A2 Receptor Antagonists
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