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Mol. Cells 2013; 36(3): 195-202

Published online August 1, 2013

https://doi.org/10.1007/s10059-013-0192-9

© The Korean Society for Molecular and Cellular Biology

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Hyung Wook Nam, Robert C. Bruner, and Doo-Sup Choi

1Department of Molecular Pharmacology and Experimental Therapeutics, 2Department of Psychiatry and Psychology, 3Molecular Neuroscience Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA

Received: July 3, 2013; Accepted: July 6, 2013

Abstract

Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

Keywords A2AR, adenosine, alcohol use disorders, caffeine, ENT1, goal-directed behavior

Article

Minireview

Mol. Cells 2013; 36(3): 195-202

Published online September 30, 2013 https://doi.org/10.1007/s10059-013-0192-9

Copyright © The Korean Society for Molecular and Cellular Biology.

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Hyung Wook Nam, Robert C. Bruner, and Doo-Sup Choi

1Department of Molecular Pharmacology and Experimental Therapeutics, 2Department of Psychiatry and Psychology, 3Molecular Neuroscience Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA

Received: July 3, 2013; Accepted: July 6, 2013

Abstract

Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

Keywords: A2AR, adenosine, alcohol use disorders, caffeine, ENT1, goal-directed behavior

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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