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An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in Drosophila
Published on: April 15, 2015
Using C. elegans to screen for targets of ethanol and behavior-altering drugs
Andrew G. Davies1, Steven L. McIntire
1Ernest Gallo Clinic and Research Center, Department of Neurology, Programs in Neuroscience and Biomedical Science, University of California, San Francisco. 5858 Horton Street, Suite 200, Emeryville, California 94608. USA.
Abstract:
Caenorhabditis elegans is an attractive model system for determining the targets of neuroactive compounds. Genetic screens in C. elegans provide a relatively unbiased approach to the identification of genes that are essential for behavioral effects of drugs and neuroactive compounds such as alcohol. Much work in vertebrate systems has identified multiple potential targets of ethanol but which, if any, of those candidates are responsible for the behavioral effects of alcohol is uncertain. Here we provide detailed methodology for a genetic screen for mutants of C. elegans that are resistant to the depressive effects of ethanol on locomotion and for the subsequent behavioral analysis of those mutants. The methods we describe should also be applicable for use in screening for mutants that are resistant or hypersensitive to many neuroactive compounds and for identifying the molecular targets or biochemical pathways mediating drug responses.
Insights
This study details a genetic screen in Caenorhabditis elegans to identify genes affecting alcohol
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Caenorhabditis elegans is a valuable model for studying neuroactive compounds.
- Identifying specific targets of ethanol's behavioral effects in vertebrates remains challenging.
- Genetic screens offer an unbiased method to find genes involved in drug responses.
Purpose of the Study:
- To present a detailed methodology for a genetic screen in C. elegans.
- To identify mutants resistant to ethanol's depressive effects on locomotion.
- To establish a framework for analyzing drug-induced behavioral changes.
Main Methods:
- Utilizing genetic screening in C. elegans to isolate ethanol-resistant mutants.
- Performing behavioral analysis to assess locomotion in identified mutants.
- Developing a reproducible methodology applicable to various neuroactive compounds.
Main Results:
- Established a detailed protocol for genetic screening of ethanol-insensitive mutants.
- Demonstrated the applicability of the methodology for behavioral analysis.
- Provided a foundation for future research into drug targets.
Conclusions:
- The described genetic screening method is effective for identifying C. elegans mutants resistant to ethanol.
- This approach can be adapted to discover genes and pathways mediating responses to diverse neuroactive compounds.
- The methodology facilitates the identification of molecular targets for drug action.

