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The Journal of Neuroscience, February 28, 2007, 27(9):2410-2415; doi:10.1523/JNEUROSCI.5066-06.2007

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Behavioral/Systems/Cognitive
Sleep Deprivation Increases A₁ Adenosine Receptor Binding in the Human Brain: A Positron Emission Tomography Study

David Elmenhorst,¹ Philipp T. Meyer,¹ Oliver H. Winz,¹ Andreas Matusch,¹ Johannes Ermert,² Heinz H. Coenen,^2,3 Radhika Basheer,⁴ Helmut L. Haas,⁵ Karl Zilles,^1,3 and Andreas Bauer^1,3

¹Institute of Medicine and ²Institute of Nuclear Chemistry, Research Center Juelich, 52425 Juelich, Germany, ³Brain Imaging Center West, 52425 Juelich, Germany, ⁴Department of Psychiatry, Veterans Affairs Boston Healthcare System–Harvard Medical School, West Roxbury, Massachusetts 02132, and ⁵Institute of Neurophysiology, Heinrich Heine University, 40225 Duesseldorf, Germany

Correspondence should be addressed to Dr. Andreas Bauer, Institute of Medicine, Research Center Juelich, 52425 Juelich, Germany. Email: an.bauer{at}fz-juelich.de

It is currently hypothesized that adenosine is involved in the induction of sleep after prolonged wakefulness. This effect is partially reversed by the application of caffeine, which is a nonselective blocker of adenosine receptors. Here, we report that the most abundant and highly concentrated A₁ subtype of cerebral adenosine receptors is upregulated after 24 h of sleep deprivation. We used the highly selective A₁ adenosine receptor (A₁AR) radioligand [¹⁸F]CPFPX ([¹⁸F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine) and quantitative positron emission tomography to assess cerebral A₁ARs before and after sleep deprivation in 12 healthy volunteers and a control group (n = 10) with regular sleep. In sleep deprived subjects, we found an increase of the apparent equilibrium total distribution volume in a region-specific pattern in all examined brain regions with a maximum increase in the orbitofrontal cortex (15.3%; p = 0.014). There were no changes in the control group with regular sleep. This is the first molecular imaging study that provides in vivo evidence for an A₁AR upregulation in cortical and subcortical brain regions after prolonged wakefulness, indicating that A₁AR expression is contributing to the homeostatic sleep regulation.

Key words: imaging; adenosine A₁ receptor; positron emission tomography; [¹⁸F]CPFPX; sleep deprivation; human

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Received Nov. 22, 2006; revised Jan. 11, 2007; accepted Jan. 29, 2007.

Correspondence should be addressed to Dr. Andreas Bauer, Institute of Medicine, Research Center Juelich, 52425 Juelich, Germany. Email: an.bauer{at}fz-juelich.de

This article has been cited by other articles:

				E. E. Benarroch Adenosine and its receptors: Multiple modulatory functions and potential therapeutic targets for neurologic disease Neurology, January 15, 2008; 70(3): 231 - 236. [Full Text] [PDF]

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