title: The genetic relationships between ethanol preference, acute ethanol sensitivity, and ethanol tolerance in Drosophila melanogaster.
abstract: The relationship between alcohol consumption, sensitivity, and tolerance is an important question that has been addressed in humans and rodent models. Studies have shown that alcohol consumption and risk of abuse may correlate with (1) increased sensitivity to the stimulant effects of alcohol, (2) decreased sensitivity to the depressant effects of alcohol, and (3) increased alcohol tolerance. However, many conflicting results have been observed. To complement these studies, we utilized a different organism and approach to analyze the relationship between ethanol consumption and other ethanol responses. Using a set of 20 Drosophila melanogaster mutants that were isolated for altered ethanol sensitivity, we measured ethanol-induced hyperactivity, ethanol sedation, sedation tolerance, and ethanol consumption preference. Ethanol preference showed a strong positive correlation with ethanol tolerance, consistent with some rodent and human studies, but not with ethanol hyperactivity or sedation. No pairwise correlations were observed between ethanol hyperactivity, sedation, and tolerance. The evolutionary conservation of the relationship between tolerance and ethanol consumption in flies, rodents, and humans indicates that there are fundamental biological mechanisms linking specific ethanol responses.
authors.affiliation: University of California, San Francisco, San Francisco, CA, USA. anita.devineni@ucsf.edu
authors.forename: Anita V
authors.initials: AV
authors.lastname: Devineni
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: McClure
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Guarnieri
authors.forename: Ammon B
authors.initials: AB
authors.lastname: Corl
authors.forename: Fred W
authors.initials: FW
authors.lastname: Wolf
authors.forename: Mark
authors.initials: M
authors.lastname: Eddison
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000435:Alcoholic Intoxication / Q000235:genetics*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005518:Food Preferences; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D014157:Transcription Factors; D000431:Ethanol