title: Acute ethanol responses in Drosophila are sexually dimorphic.
abstract: In mammalian and insect models of ethanol intoxication, low doses of ethanol stimulate locomotor activity whereas high doses induce sedation. Sex differences in acute ethanol responses, which occur in humans, have not been characterized in Drosophila. In this study, we find that male flies show increased ethanol hyperactivity and greater resistance to ethanol sedation compared with females. We show that the sex determination gene transformer (tra) acts in the developing nervous system, likely through regulation of fruitless (fru), to at least partially mediate the sexual dimorphism in ethanol sedation. Although pharmacokinetic differences may contribute to the increased sedation sensitivity of females, neuronal tra expression regulates ethanol sedation independently of ethanol pharmacokinetics. We also show that acute activation of fru-expressing neurons affects ethanol sedation, further supporting a role for fru in regulating this behavior. Thus, we have characterized previously undescribed sex differences in behavioral responses to ethanol, and implicated fru in mediating a subset of these differences.
authors.affiliation: Program in Neuroscience and Department of Anatomy, University of California, San Francisco, CA 94158, USA. ad3030@columbia.edu
authors.forename: Anita V
authors.initials: AV
authors.lastname: Devineni
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
mesh_terms: D000435:Alcoholic Intoxication; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000378:metabolism*; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D015233:Models, Statistical; D009474:Neurons / Q000187:drug effects; D012727:Sex Characteristics; D012737:Sex Factors
chemical_list: D000697:Central Nervous System Stimulants; D000431:Ethanol