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An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in Drosophila

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Published on: April 15, 2015

Tph2 Gene Expression Defines Ethanol Drinking Behavior in Mice.

Magdalena Zaniewska^1,2, Valentina Mosienko¹, Michael Bader^1,3,4,5

¹Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.

|March 10, 2022

Summary

Reduced brain serotonin (5-hydroxytryptamine; 5-HT) signaling increases ethanol consumption in mice. This study shows central 5-HT modulates alcohol drinking but is not essential for ethanol

Keywords:

Tph2 knockout Tph2 transcript central 5-HT ethanol mice raphe nuclei

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Area of Science:

Neuroscience
Pharmacology
Genetics

Background:

Indirect evidence links disrupted serotonin (5-hydroxytryptamine; 5-HT) signaling to addictive behaviors.
The precise role of central 5-HT in ethanol consumption remains unclear due to contradictory findings.

Purpose of the Study:

To investigate the role of central serotonin (5-HT) in modulating alcohol drinking behavior.
To assess the necessity of central 5-HT for the antidepressant effects of ethanol.

Main Methods:

Utilized mice genetically engineered to be deficient in tryptophan hydroxylase 2 (Tph2-/-), lacking central 5-HT synthesis.
Assessed ethanol consumption using a two-bottle choice test and antidepressant-like effects via the forced swim test.
Analyzed Tph2 gene expression in the brain in relation to ethanol intake.

Main Results:

Life-long 5-HT depletion in Tph2-/- mice significantly increased ethanol consumption compared to wild-type controls.
While naïve Tph2-/- mice showed increased water intake, ethanol exposure normalized this to wild-type levels.
Tph2 deficiency did not alter the antidepressant response to ethanol in the forced swim test.
Tph2 gene expression did not change with ethanol consumption in wild-type mice, but inter-individual intake correlated with Tph2 levels.

Conclusions:

Central serotonin (5-HT) is a critical modulator of ethanol drinking behavior in mice.
The antidepressant effects of ethanol do not depend on the presence of central 5-HT.