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Modulation of voluntary ethanol consumption by beta-arrestin 2.

K Björk¹, R Rimondini, A C Hansson

¹Laboratory of Clinical and Translational Studies, NIAAA/NIH, 10 Center Dr., Bethesda, MD 20892-1108, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology

|March 28, 2008

Summary

Beta-arrestin 2 (Arrb2) influences ethanol reward and consumption. Genetic variations in Arrb2 impact its expression, affecting responses to alcohol.

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Area of Science:

Neuroscience
Genetics
Pharmacology

Background:

Beta-arrestin 2 (Arrb2) is crucial for G protein-coupled receptor signaling, including pathways involved in ethanol's rewarding effects.
Mu-opiate and dopamine D2 receptor signaling are implicated in mediating ethanol reward.

Purpose of the Study:

To investigate the role of beta-arrestin 2 (Arrb2) in ethanol consumption and reward.
To identify genetic factors influencing Arrb2 expression in the context of ethanol preference.

Main Methods:

Compared Arrb2 gene and protein expression in ethanol-preferring (AA) rats versus non-preferring (ANA) rats.
Analyzed Arrb2 gene variants and quantitative trait loci associated with expression.
Validated findings using Arrb2-deficient mice to assess ethanol consumption and behavioral responses.

Main Results:

Elevated Arrb2 expression was found in the striatum and hippocampus of ethanol-preferring rats.
A specific haplotype and a quantitative trait locus linked to Arrb2 expression were identified.
Arrb2-deficient mice showed reduced ethanol intake and psychomotor stimulation.

Conclusions:

Beta-arrestin 2 (Arrb2) plays a significant role in modulating acute responses to ethanol.
Genetic variation in Arrb2 contributes to individual differences in ethanol reward and consumption.