The biological basis of ethanol tolerance in Drosophila

Geer, Billy W.; Heinstra, Pieter W. H.; McKechnie, Stephen William

doi:10.1016/0305-0491(93)90221-p

Cited by 60 publications

(70 citation statements)

References 162 publications

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“…The latter has been used to describe the flies' ability to withstand the toxic effects of ethanol (reviewed in Geer et al, 1993). The assays usually involve growing flies continuously on culture medium containing relatively high concentrations (up to 10%) of ethanol, and by measuring the rate of survival to the adult stage.…”

Section: Ethanol Tolerance In Drosophilamentioning

confidence: 99%

“…The assays usually involve growing flies continuously on culture medium containing relatively high concentrations (up to 10%) of ethanol, and by measuring the rate of survival to the adult stage. This form of tolerance is thought to rely primarily on enzymatic or cellular functions that contribute to metabolism and/or elimination of ethanol (reviewed in Geer et al, 1993). For example, expression of the ethanol metabolizing enzyme alcohol dehydrogenase (ADH) is induced by ethanol in larvae (but not adults).…”

Section: Ethanol Tolerance In Drosophilamentioning

confidence: 99%

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Invertebrate models of drug abuse

2002

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Susceptibility to drug addiction depends on genetic and environmental factors and their complex interactions. Studies with mammalian models have identified molecular targets, neurochemical systems, and brain regions that mediate some of the addictive properties of abused drugs. Yet, our understanding of how the primary effects of drugs lead to addiction remains incomplete. Recently, researchers have turned to the invertebrate model systems Drosophila melanogaster and Caenorhabditis elegans to dissect the mechanisms by which abused drugs modulate behavior. Due to their sophisticated genetics, relatively simple anatomy, and their remarkable molecular similarity to mammals, these invertebrate models should provide useful insights into the mechanisms of drug action. Here we review recent behavioral and genetic studies in flies and worms on the effects of ethanol, cocaine, and nicotine, three of the most widely abused drugs in the world.

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Section: Ethanol Tolerance In Drosophilamentioning

confidence: 99%

Section: Ethanol Tolerance In Drosophilamentioning

confidence: 99%

Invertebrate models of drug abuse

2002

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“…For example, adult flies allowed to mate on ethanolcontaining media improve mating success and fecundity (8). Although rearing larvae on food containing relatively high ethanol concentrations delays development and decreases survival (9-11), larvae reared on low concentrations of ethanol develop into heavier adults (7,12). This weight increase may be a result of D. melanogaster larvae metabolizing ethanol and using it as a food source (12).…”

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confidence: 99%

“…Although rearing larvae on food containing relatively high ethanol concentrations delays development and decreases survival (9)(10)(11), larvae reared on low concentrations of ethanol develop into heavier adults (7,12). This weight increase may be a result of D. melanogaster larvae metabolizing ethanol and using it as a food source (12). Ingestion of ethanol during the larval stage has additional benefits, such as protection from natural parasites such as endoparasitoid wasps (13).…”

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confidence: 99%

Competing dopamine neurons drive oviposition choice for ethanol in Drosophila

Azanchi

Kaun

Heberlein

2013

Proc. Natl. Acad. Sci. U.S.A.

101

100

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The neural circuits that mediate behavioral choice evaluate and integrate information from the environment with internal demands and then initiate a behavioral response. Even circuits that support simple decisions remain poorly understood. In Drosophila melanogaster, oviposition on a substrate containing ethanol enhances fitness; however, little is known about the neural mechanisms mediating this important choice behavior. Here, we characterize the neural modulation of this simple choice and show that distinct subsets of dopaminergic neurons compete to either enhance or inhibit egg-laying preference for ethanol-containing food. Moreover, activity in α′β′ neurons of the mushroom body and a subset of ellipsoid body ring neurons (R2) is required for this choice. We propose a model where competing dopaminergic systems modulate oviposition preference to adjust to changes in natural oviposition substrates.I n nature, rotting fruit is the social hub for the fruit fly Drosophila melanogaster. Flies use fermenting fruit as a food source (1) and a site for oviposition (2). The choice of a suitable oviposition substrate is an ecologically important decision with a direct impact on species fitness. However, other than having a clear preference for fermenting fruit, how females choose oviposition sites in nature is largely unknown.One of the main metabolites of fermentation is ethanol, which is present in ripe fleshy fruits (3). Although ethanol concentrations in the fruit are rather low [≤5% (vol/vol)] (4), plumes containing ethanol vapor can act as long-distance signals to attract flies to rotting fruit (3, 5). When given the choice, female flies prefer to lay their eggs on media containing low concentrations of ethanol (up to 5%) (6), which leads to enhanced fitness of the developing larva and the adult fly.D. melanogaster's resistance to ethanol toxicity may have evolved to allow inhabitation of ethanol-containing environments (7). For example, adult flies allowed to mate on ethanolcontaining media improve mating success and fecundity (8). Although rearing larvae on food containing relatively high ethanol concentrations delays development and decreases survival (9-11), larvae reared on low concentrations of ethanol develop into heavier adults (7,12). This weight increase may be a result of D. melanogaster larvae metabolizing ethanol and using it as a food source (12). Ingestion of ethanol during the larval stage has additional benefits, such as protection from natural parasites such as endoparasitoid wasps (13).Studies on the neural circuits underlying the oviposition program and choice of oviposition substrates have been initiated only recently in D. melanogaster (14, 15). Ethanol is a particularly intriguing stimulus for oviposition preference, because it has, depending on concentration, both beneficial and detrimental effects on developing larvae. In flies, the function of dopaminergic neurons has been implicated in responses to both rewarding and aversive stimuli (16-19), making it a candidate neuromodulator to signa...

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“…T HE genus Drosophila has an evolutionary history of exposure to alcohols, and it is believed that the adaptation to alcohols has facilitated the cosmopolitan spread of Drosophila melanogaster to temperate environments (Geer et al 1993). Both larval and adult fruit flies feed on yeast, and this ecological niche exposes them to toxic fermentation products, including alcohols.…”

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Direct Evidence That Genetic Variation in Glycerol-3-Phosphate and Malate Dehydrogenase Genes (Gpdh and Mdh1) Affects Adult Ethanol Tolerance in Drosophila melanogaster

et al. 2009

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Many studies of alcohol adaptation in Drosophila melanogaster have focused on the Adh polymorphism, yet the metabolic elimination of alcohol should involve many enzymes and pathways. Here we evaluate the effects of glycerol-3-phosphate dehydrogenase (Gpdh) and cytosolic malate dehydrogenase (Mdh1) genotype activity on adult tolerance to ethanol. We have created a set of P-element-excision-derived Gpdh, Mdh1, and Adh alleles that generate a range of activity phenotypes from full to zero activity. Comparisons of paired Gpdh genotypes possessing 10 and 60% normal activity and 66 and 100% normal activity show significant effects where higher activity increases tolerance. Mdh1 null allele homozygotes show reductions in tolerance. We use piggyBac FLP-FRT site-specific recombination to create deletions and duplications of Gpdh. Duplications show an increase of 50% in activity and an increase of adult tolerance to ethanol exposure. These studies show that the molecular polymorphism associated with GPDH activity could be maintained in natural populations by selection related to adaptation to alcohols. Finally, we examine the interactions between activity genotypes for Gpdh, Mdh1, and Adh. We find no significant interlocus interactions. Observations on Mdh1 in both Gpdh and Adh backgrounds demonstrate significant increases in ethanol tolerance with partial reductions (50%) in cytosolic MDH activity. This observation strongly suggests the operation of pyruvatemalate and, in particular, pyruvate-citrate cycling in adaptation to alcohol exposure. We propose that an understanding of the evolution of tolerance to alcohols will require a system-level approach, rather than a focus on single enzymes.

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The biological basis of ethanol tolerance in Drosophila

Cited by 60 publications

References 162 publications

Invertebrate models of drug abuse

Invertebrate models of drug abuse

Competing dopamine neurons drive oviposition choice for ethanol in Drosophila

Direct Evidence That Genetic Variation in Glycerol-3-Phosphate and Malate Dehydrogenase Genes (Gpdh and Mdh1) Affects Adult Ethanol Tolerance in Drosophila melanogaster

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