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An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in Drosophila
Published on: April 15, 2015
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The hangover gene defines a stress pathway required for ethanol tolerance development
Henrike Scholz1, Mirjam Franz, Ulrike Heberlein
1Department of Anatomy, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. henrike.scholz@biozentrum.uni-wuerzburg.de
Nature
|August 12, 2005
Summary
A new gene, hangover, is essential for developing alcohol tolerance in fruit flies. This discovery reveals two distinct pathways involved in tolerance, including a cellular stress response, suggesting conserved mechanisms across species.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Repeated alcohol consumption induces tolerance, physical dependence, and addiction.
- Drosophila melanogaster serves as a model organism, exhibiting ethanol tolerance with kinetics similar to mammals.
- This tolerance is known to involve the catecholamine octopamine, the functional analog of mammalian noradrenaline.
Purpose of the Study:
- To identify novel genetic factors involved in the development of ethanol tolerance.
- To elucidate the molecular pathways underlying ethanol tolerance in Drosophila.
- To investigate the role of cellular stress responses in drug tolerance.
Main Methods:
- Genetic screens in Drosophila to identify mutations affecting ethanol tolerance.
- Behavioral assays to measure ethanol tolerance and responses to environmental stressors (heat, paraquat).
- Genetic epistasis tests to determine the relationship between genes and pathways.
Main Results:
- A new gene, hangover, was identified as crucial for normal ethanol tolerance development.
- hangover mutants exhibited defects in responses to various environmental stressors.
- Ethanol tolerance in Drosophila was shown to depend on two distinct pathways: a cellular stress pathway involving hangover and a parallel pathway involving octopamine.
- hangover encodes a nuclear zinc-finger protein, indicating a potential role in nucleic acid binding.
Conclusions:
- Ethanol tolerance in Drosophila is regulated by at least two parallel molecular pathways.
- A cellular stress response pathway, mediated by the hangover gene, plays a significant role in ethanol tolerance.
- The findings suggest that conserved evolutionary mechanisms link cellular stress responses to drug tolerance and addiction-related behaviors.
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