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ISSN: 2155-6105

Journal of Addiction Research & Therapy
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Research Article

Sex-Specific Regulation of Depression, Anxiety-Like Behaviors and Alcohol Drinking in Mice Lacking ENT1

Christina L. Ruby1, Denise L. Walker2, Joyce An1, Jason Kim1 and Doo-Sup Choi1,2*

1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, USA

2Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, USA

*Corresponding Author:
Doo-Sup Choi, Ph.D
Department of Molecular Pharmacology and Experimental Therapeutics
Mayo Clinic College of Medicine, 200 First Street SW
Rochester, Minnesota 55905, USA
Tel: (507) 284-5602
Fax: (507) 266-0824
E-mail: [email protected]

Received November 08, 2011; Accepted December 21, 2011; Published December 25, 2011

Citation: Ruby CL, Walker DL, An J, Kim J, Choi DS (2011) Sex-Specific Regulation of Depression, Anxiety-Like Behaviors and Alcohol Drinking in Mice Lacking ENT1. J Addict Res Ther S4:004. doi:10.4172/2155-6105.S4-004

Copyright: © 2011 Ruby CL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Objectives: Adenosine signaling has been implicated in the pathophysiology of several psychiatric disorders including alcoholism, depression, and anxiety. Adenosine levels are controlled in part by transport across the cell membrane by equilibrative nucleoside transporters (ENTs). Recent evidence showed that a polymorphism in the gene encoding ENT1 is associated with comorbid depression and alcoholism in women. We have previously shown that deletion of ENT1 reduces ethanol intoxication and elevates alcohol intake in mice. Interestingly, ENT1 null mice display decreased anxiety-like behavior compared to wild-type littermates. However, our behavioral studies were performed only in male mice. Here, we extend our research to include female mice, and test the effect of ENT1 knockout on other behavioral correlates of alcohol drinking, including depressive and compulsive behavior, in mice.

Methods: To assess depression-like behavior, we used a forced swim test modified for mice. We examined anxiety-like behavior and locomotor activity in open field chambers, and perseverant behavior using the marble-burying test. Finally, we investigated alcohol consumption and preference in female mice using a two-bottle choice paradigm.

Results: ENT1 null mice of both sexes showed reduced immobility time in the forced swim test and increased time in the center of the open field compared to wild-type littermates. ENT1 null mice of both sexes showed similar locomotor activity levels and habituation to the open field chambers. Female ENT1 null mice displayed increased marble-burying compared to female wild-types, but no genotype difference was evident in males. Female ENT1 null mice showed increased ethanol consumption and preference compared to female wild-types.

Conclusions: Our findings suggest that ENT1 contributes to several important behaviors involved in psychiatric disorders. Inhibition of ENT1 may be beneficial in treating depression and anxiety, while enhancement of ENT1 function may reduce compulsive behavior and drinking, particularly in females.


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