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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


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.


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

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


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