title: Mutations in the circadian gene period alter behavioral and biochemical responses to ethanol in Drosophila.
abstract: Clock genes, such as period, which maintain an organism's circadian rhythm, can have profound effects on metabolic activity, including ethanol metabolism. In turn, ethanol exposure has been shown in Drosophila and mammals to cause disruptions of the circadian rhythm. Previous studies from our labs have shown that larval ethanol exposure disrupted the free-running period and period expression of Drosophila. In addition, a recent study has shown that arrhythmic flies show no tolerance to ethanol exposure. As such, Drosophila period mutants, which have either a shorter than wild-type free-running period (perS) or a longer one (perL), may also exhibit altered responses to ethanol due to their intrinsic circadian differences. In this study, we tested the initial sensitivity and tolerance of ethanol exposure on Canton-S, perS, and perL, and then measured their Alcohol Dehydrogenase (ADH) and body ethanol levels. We showed that perL flies had slower sedation rate, longer recovery from ethanol sedation, and generated higher tolerance for sedation upon repeated ethanol exposure compared to Canton-S wild-type flies. Furthermore, perL flies had lower ADH activity and had a slower ethanol clearance compared to wild-type flies. The findings of this study suggest that period mutations influence ethanol induced behavior and ethanol metabolism in Drosophila and that flies with longer circadian periods are more sensitive to ethanol exposure.
authors.affiliation: Department of Biology, 5720 Mayflower Hill Dr., Colby College, Waterville, ME 04901, USA. Electronic address: Jennifer_liao@dfci.harvard.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Biological Sciences, 24 Park Ave., Bridgewater State University, Bridgewater, MA 02325, USA. Electronic address: joseph.seggio@bridgew.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Seggio
authors.affiliation: Department of Biology, 5720 Mayflower Hill Dr., Colby College, Waterville, ME 04901, USA. Electronic address: stahmad@colby.edu.
authors.forename: S Tariq
authors.initials: ST
authors.lastname: Ahmad
mesh_terms: D000367:Age Factors; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics
chemical_list: D002492:Central Nervous System Depressants; D029721:Drosophila Proteins; D056950:Period Circadian Proteins; D000431:Ethanol; D000426:Alcohol Dehydrogenase
keywords: Alcoholism; Circadian rhythm; Drosophila; Ethanol; period