Long-Term Functional Side-Effects of Stimulants and Sedatives in Drosophila melanogaster 英文参考文献.docVIP

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Long-Term Functional Side-Effects of Stimulants and Sedatives in Drosophila melanogaster 英文参考文献.doc

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Long-Term Functional Side-Effects of Stimulants and Sedatives in Drosophila melanogaster 英文参考文献

Long-TermFunctionalSide-EffectsofStimulantsand SedativesinDrosophilamelanogaster KennedyMatsagas,DavidB.Lim,MarcHorwitz,CristinaL.Rizza,LaurenceD.Mueller,Bryant Villeponteau,MichaelR.Rose* GenescientCorporation,CoronaDelMar,California,UnitedStatesofAmerica Abstract Background:Smallinvertebrateanimals,suchasnematodesandfruitflies,areincreasinglybeingusedtotestcandidate drugs both for specific therapeutic purposes and for long-term health effects. Some of the protocols used in these experimentsfeaturesuchexperimentaldesignfeaturesaslifelongvirginityandverylowdensities.Bycontrast,theabilityof bothfruitfliesandnematodestoresiststressisfrequentlycorrelatedwiththeirlongevityandotherfunctionalmeasures, suggestingthatlow-stressassaysarenotnecessarilytheonlyusefulprotocolfortestingthelong-termeffectsofdrugs. Methodology/Principal Findings: Here we report an alternative protocol for fruit fly drug-testing that maximizes reproductive opportunities and other types of interaction, with moderately high population densities. We validate this protocolusingtwotypesofexperimentaltests:1.Weshowthatthisprotocoldetectspreviouslywell-establishedgenetic differencesbetweenoutbredfruitflypopulations.2.Weshowthatthisprotocolisabletodistinguishamongthelong-term effectsofsimilartypesofdrugswithintwobroadcategories,stimulantsandtranquilizers. Conclusions: Large-scale fly drug testing can be conducted using mixed-sex high-density cage assays. We find that the commonly-used stimulants caffeine and theobromine differ dramatically in their chronic functional effects, theobromine beingmorebenign.Likewise,wefindthattwogenericpharmaceuticaltranquilizers,lithiumcarbonateandvalproicacid, differdramaticallyintheirchroniceffects,lithiumbeingmorebenign.However,thesefindingsdonotnecessarilyapplyto humansubjects,andwethusdonotrecommendtheuseofanyonesubstanceoveranyother. Citation: Matsagas K, Lim DB, Horwitz M, Rizza CL, Mueller LD, et al. (2009) Long-Term Functional Side-Effects of Stimulants and Sedative