Adenosine A1 and A2A receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal

Christa J. Van Dort, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

93 Citations (Scopus)

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 A1 and A2A 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 A1 receptor antagonist into the prefrontal cortex. The results showed that adenosine A1 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 A1 receptors within the prefrontal cortex comprise part of a descending system that inhibits wakefulness.

Original languageEnglish (US)
Pages (from-to)871-881
Number of pages11
JournalJournal of Neuroscience
Volume29
Issue number3
DOIs
StatePublished - Jan 21 2009

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Adenosine A2A Receptors
Adenosine A1 Receptors
Arousal
Prefrontal Cortex
Acetylcholine
Purinergic P1 Receptors
Wakefulness
Sleep
Brain
Adenosine
Xanthines
Adenosine A1 Receptor Antagonists
Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Microdialysis
Prosencephalon
Caffeine
Brain Stem
Neurotransmitter Agents
Dialysis

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Adenosine A1 and A2A receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. / Van Dort, Christa J.; Baghdoyan, Helen; Lydic, Ralph.

In: Journal of Neuroscience, Vol. 29, No. 3, 21.01.2009, p. 871-881.

Research output: Contribution to journalArticle

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