Cited by 143Sleep and Wakefulness ResearchAdenosine and Purinergic SignalingNeurotransmitter Receptor Influence on Behavior

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Adenosine A 1 and A 2A Receptors in Mouse Prefrontal Cortex Modulate Acetylcholine Release and Behavioral Arousal

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Van Dort, Christa J., Baghdoyan, Helen A., Lydic, Ralph·2009·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.4111-08.2009

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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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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
Published
2009-01-21
Volume
29
Issue
3
Pages
871-881
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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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