The Genetics of Alcohol Responses of Invertebrate Model Systems

Rothenfluh, Adrian; Troutwine, Benjamin R; Ghezzi, Alfredo; Atkinson, Nigel S.

doi:10.1016/b978-0-12-405941-2.00023-7

Cited by 11 publications

(11 citation statements)

References 199 publications

(245 reference statements)

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“…This ethanol sedation assay is similar to and to a large extent based on previously reported methods ( e.g. 6,20,25-27 , comprehensively reviewed in 3,28 ). Although all of these assays have utility for measuring ethanol sedation sensitivity, advantages of the assay described here include (i) flies are not exposed to liquid ethanol during the assay, (ii) the reduced possibility that flies can become entangled in cotton or other material in the testing vial during the assay, (iii) the ability to test many groups of flies in parallel, and (iv) three options for the objective quantification of ethanol sensitivity from primary data sets.…”

Section: Discussionsupporting

confidence: 58%

An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in <em>Drosophila</em>

Sandhu

Kollah

Lewellyn

et al. 2015

JoVE

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Alcohol use disorder (AUD) is a serious health challenge. Despite a large hereditary component to AUDs, few genes have been unambiguously implicated in their etiology. The fruit fly, Drosophila melanogaster, is a powerful model for exploring molecular-genetic mechanisms underlying alcohol-related behaviors and therefore holds great promise for identifying and understanding the function of genes that influence AUD. The use of the Drosophila model for these types of studies depends on the availability of assays that reliably measure behavioral responses to ethanol. This report describes an assay suitable for assessing ethanol sensitivity and rapid tolerance in flies. Ethanol sensitivity measured in this assay is influenced by the volume and concentration of ethanol used, a variety of previously reported genetic manipulations, and also the length of time the flies are housed without food immediately prior to testing. In contrast, ethanol sensitivity measured in this assay is not affected by the vigor of fly handling, sex of the flies, and supplementation of growth medium with antibiotics or live yeast. Three different methods for quantitating ethanol sensitivity are described, all leading to essentially indistinguishable ethanol sensitivity results. The scalable nature of this assay, combined with its overall simplicity to set-up and relatively low expense, make it suitable for small and large scale genetic analysis of ethanol sensitivity and rapid tolerance in Drosophila.

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Section: Discussionsupporting

confidence: 58%

An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in <em>Drosophila</em>

Sandhu

Kollah

Lewellyn

et al. 2015

JoVE

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“…Behavioral responses to acute alcohol exposure in iMOs and humans are also conserved overall (Devineni and Heberlein, 2013; Rothenfluh et al, 2014). Low doses of alcohol elicit locomotor or psychomotor stimulation, while moderate doses of alcohol produce sedation in flies, worms, and humans.…”

Section: Invertebrate Model In Alcohol Researchmentioning

confidence: 99%

“…Rapid tolerance to alcohol can be measured by assessing the ability of the drug to sedate flies during 2 alcohol exposures separated by a recovery period (flies are more resistant during the second exposure due to adaptations in the nervous system) (e.g., Bhandari et al, 2009; Chan et al, 2014; Cowmeadow et al, 2005; Scholz et al, 2000). Readers are directed to several comprehensive reviews on Drosophila as a model for alcohol behavior for additional details and discussion (Devineni and Heberlein, 2013; Kaun et al, 2012; Morozova et al, 2012; Robinson and Atkinson, 2013; Rodan and Rothenfluh, 2010b; Rothenfluh et al, 2014; Scholz and Mustard, 2011). …”

Section: Invertebrate Model In Alcohol Researchmentioning

confidence: 99%

“…To compile all genetic manipulations (and therefore genes) that are important for alcohol-related behavior in flies and worms, we performed extensive searches of PubMed through 2014 (using combinations of the search terms EtOH, alcohol, Drosophila , C. elegans , names of individual investigators, etc.) and supplemented these searches with lists of genes obtained from several recent reviews (Davies and Bettinger, 2014; Kaun et al, 2012; Morozova et al, 2012; Rodan and Rothenfluh, 2010a; Rothenfluh et al, 2014) in addition to a recent publication from one of the authors (Mathies et al, 2015). Together, studies in flies and worms have identified 91 and 50 genes, respectively, that influence behavioral responses to alcohol (Tables 1 and 2).…”

Section: Invertebrate Model In Alcohol Researchmentioning

confidence: 99%

“…Additionally, these gene products participate in histone deacetylation ( Sir2 family), alcohol metabolism ( Adh / sodh-1 family), and dopamine signaling (Dop1R1 / dop-4 family) or have incompletely characterized functions ( Clic family). Readers are referred to several excellent recent reviews for additional details on the molecular function of the genes in flies and worms (Davies and Bettinger, 2014; Kaun et al, 2012; Morozova et al, 2012; Rodan and Rothenfluh, 2010a; Rothenfluh et al, 2014). …”

Section: Invertebrate Model In Alcohol Researchmentioning

confidence: 99%

See 2 more Smart Citations

DrosophilaandCaenorhabditis elegansas Discovery Platforms for Genes Involved in Human Alcohol Use Disorder

Grotewiel

Bettinger

2015

Alcohol Clin Exp Res

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Background Despite the profound clinical significance and strong heritability of alcohol use disorder (AUD), we do not yet have a comprehensive understanding of the naturally occurring genetic variance within the human genome that drives its development. This lack of understanding is likely to be due in part to the large phenotypic and genetic heterogeneities that underlie human AUD. As a complement to genetic studies in humans, many laboratories are using the invertebrate model organisms (iMOs) Drosophila melanogaster (fruit fly) and Caenorhabditis elegans (nematode worm) to identify genetic mechanisms that influence the effects of alcohol (ethanol) on behavior. While these extremely powerful models have identified many genes that influence the behavioral responses to alcohol, in most cases it has remained unclear whether results from behavioral–genetic studies in iMOs are directly applicable to understanding the genetic basis of human AUD. Methods In this review, we critically evaluate the utility of the fly and worm models for identifying genes that influence AUD in humans. Results Based on results published through early 2015, studies in flies and worms have identified 91 and 50 genes, respectively, that influence 1 or more aspects of behavioral responses to alcohol. Collectively, these fly and worm genes correspond to 293 orthologous genes in humans. Intriguingly, 51 of these 293 human genes have been implicated in AUD by at least 1 study in human populations. Conclusions Our analyses strongly suggest that the Drosophila and C. elegans models have considerable utility for identifying orthologs of genes that influence human AUD.

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Molecular mechanisms underlying alcohol-drinking behaviours

2016

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The main characteristic of alcohol use disorder is the consumption of large quantities of alcohol despite the negative consequences. The transition from the moderate use of alcohol to excessive, uncontrolled alcohol consumption results from neuroadaptations that cause aberrant motivational learning and memory processes. Here, we examine studies that have combined molecular and behavioural approaches in rodents to elucidate the molecular mechanisms that keep the social intake of alcohol in check, which we term ‘stop pathways’, and the neuroadaptations that underlie the transition from moderate to uncontrolled, excessive alcohol intake, which we term ‘go pathways’. We also discuss post-transcriptional, genetic and epigenetic alterations that underlie both types of pathways.

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The Genetics of Alcohol Responses of Invertebrate Model Systems

Cited by 11 publications

References 199 publications

An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in <em>Drosophila</em>

An Inexpensive, Scalable Behavioral Assay for Measuring Ethanol Sedation Sensitivity and Rapid Tolerance in <em>Drosophila</em>

DrosophilaandCaenorhabditis elegansas Discovery Platforms for Genes Involved in Human Alcohol Use Disorder

Molecular mechanisms underlying alcohol-drinking behaviours

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