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Ethanol Preference and Drinking Behavior Are Controlled by RNA Editing in the Nucleus Accumbens
Takahira Shirahase1,2,3, Yoshihisa Watanabe1, Atsushi Tsujimura1
1Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Frontiers in Behavioral Neuroscience
|January 31, 2019
Summary
RNA editing, regulated by ADAR2 in the nucleus accumbens (NAc), influences alcohol addiction. Disrupting ADAR2 in the NAc reduces ethanol intake and preference, suggesting a role in alcohol dependence.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- RNA editing is crucial for brain function, with dysregulation linked to disorders.
- Chronic ethanol consumption increases RNA editing of the serotonin 2C receptor in the nucleus accumbens (NAc).
Purpose of the Study:
- To investigate the role of RNA editing in the NAc in modulating alcohol addiction.
- To determine if ADAR2-mediated RNA editing in the NAc affects alcohol preference and intake.
Main Methods:
- Generated NAc-specific knockout mice for ADAR2 (double-stranded RNA-specific adenosine deaminase) using AAV-GFP/Cre.
- Conducted behavioral tests including open field, anxiety/depression-like behaviors, ethanol vapor exposure, ethanol drinking, and conditioned place preference (CPP).
Main Results:
- NAc-specific ADAR2 knockout mice exhibited decreased locomotor activity but no anxiety/depression-like behaviors.
- Chronic ethanol vapor exposure-induced increases in ethanol intake and preference were significantly reduced in ADAR2 knockout mice.
Conclusions:
- ADAR2-mediated RNA editing in the NAc plays a significant role in determining alcohol preference after chronic ethanol consumption.
- Targeting ADAR2 in the NAc may offer therapeutic strategies for alcohol addiction.
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