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Updated: May 12, 2026
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Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice
Published on: January 7, 2019
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Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice
Bryan Mackowiak1, David L Haggerty2, Taylor Lehner1
1Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Alcohol, Clinical & Experimental Research
|March 21, 2025
Summary
Alcohol dehydrogenase 1 (ADH1) significantly impacts ethanol consumption and preference. Inhibiting or removing ADH1 alters ethanol metabolite levels and drinking behaviors, crucial for understanding alcohol use disorder.
Area of Science:
- Pharmacology
- Neuroscience
- Metabolism
Background:
- Ethanol metabolism is closely tied to ethanol consumption behaviors.
- Alcohol dehydrogenase (ADH) and aldehyde dehydrogenases (ALDHs) are key enzymes in ethanol breakdown.
- Understanding ethanol metabolite roles is vital for developing interventions for alcohol use disorder (AUD).
Purpose of the Study:
- To investigate how alcohol dehydrogenase 1 (ADH1) influences ethanol metabolite distribution.
- To determine ADH1's role in modulating ethanol consumption behaviors.
Main Methods:
- Utilized drinking-in-the-dark (DID) and two-bottle choice (2BC) paradigms in mice.
- Assessed ethanol metabolite concentrations and drinking microstructure via lickometry.
- Employed ADH1 inhibition (fomepizole) and Adh1-knockout (Adh1 KO) mouse models.
Main Results:
- Adh1 KO mice and those treated with ADH1 inhibitor showed reduced ethanol consumption and preference.
- Ethanol levels increased, while peripheral acetaldehyde and acetate levels were altered in Adh1 KO mice.
- Perturbations in ethanol metabolism affected drinking bout structures and temporal patterns.
Conclusions:
- ADH1-mediated ethanol metabolism is a critical factor in regulating ethanol intake.
- This study reveals a significant knowledge gap in how ethanol and its metabolites drive consumption.
- Findings provide insights into the neurobiological mechanisms underlying alcohol consumption.
