Intoxicated Fly Brains: Neurons Mediating Ethanol-Induced Behaviors

Scholz, Henrike

doi:10.1080/01677060802471676

Cited by 18 publications

(20 citation statements)

References 65 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon initial exposure to low concentrations of alcohol, flies exhibit increased locomotor activity, replaced by a lack of motor coordination, the loss of postural control and righting reflexes (Loss of Righting Reflex: LoRR), and sedation (complete lack of motor activity in response to mechanical stimulation) as exposure to alcohol progresses [4][5][6][7][8][9] . The endogenous circadian clock is a strong modulator of alcohol sensitivity and toxicity as observed in mice 10,11 , rats 12 , and humans 13 .…”

Section: Introductionmentioning

confidence: 99%

The FlyBar: Administering Alcohol to Flies

Linde

Fumagalli

Roman

et al. 2014

JoVE

View full text Add to dashboard Cite

Fruit flies (Drosophila melanogaster) are an established model for both alcohol research and circadian biology. Recently, we showed that the circadian clock modulates alcohol sensitivity, but not the formation of tolerance. Here, we describe our protocol in detail. Alcohol is administered to the flies using the FlyBar. In this setup, saturated alcohol vapor is mixed with humidified air in set proportions, and administered to the flies in four tubes simultaneously. Flies are reared under standardized conditions in order to minimize variation between the replicates. Three-day old flies of different genotypes or treatments are used for the experiments, preferably by matching flies of two different time points (e.g., CT 5 and CT 17) making direct comparisons possible. During the experiment, flies are exposed for 1 hr to the pre-determined percentage of alcohol vapor and the number of flies that exhibit the Loss of Righting reflex (LoRR) or sedation are counted every 5 min. The data can be analyzed using three different statistical approaches. The first is to determine the time at which 50% of the flies have lost their righting reflex and use an Analysis of the Variance (ANOVA) to determine whether significant differences exist between time points. The second is to determine the percentage flies that show LoRR after a specified number of minutes, followed by an ANOVA analysis. The last method is to analyze the whole times series using multivariate statistics. The protocol can also be used for non-circadian experiments or comparisons between genotypes. Video LinkThe video component of this article can be found at

show abstract

Section: Introductionmentioning

confidence: 99%

The FlyBar: Administering Alcohol to Flies

Linde

Fumagalli

Roman

et al. 2014

JoVE

View full text Add to dashboard Cite

show abstract

“…12 As with C. elegans, the fly has also been an important tool for addiction studies. 55,56 For example, using forward genetics, a mutant fly was identified that was less affected by the sedating features of alcohol. Given the colorful name happyhour, the mammalian homolog of the mutated Drosophila gene was subsequently identified, and in the process new pathways involved in addiction were revealed.…”

Section: Drosophila Melanogastermentioning

confidence: 99%

Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish?

et al. 2010

View full text Add to dashboard Cite

While the research community has accepted the value of rodent models as informative research platforms, there is less awareness of the utility of other small vertebrate and invertebrate animal models. Neuroscience is increasingly turning to smaller, non-rodent models to understand mechanisms related to neuropsychiatric disorders. Although they can never replace clinical research, there is much to be learnt from 'small brains'. In particular, these species can offer flexible genetic 'tool kits' that can be used to explore the expression and function of candidate genes in different brain regions. Very small animals also offer efficiencies with respect to high-throughput screening programs. This review provides a concise overview of the utility of models based on worm, fruit fly, honeybee and zebrafish. Although these species may have small brains, they offer the neuropsychiatric research community opportunities to explore some of the most important research questions in our field.

show abstract

“…The most promising finding, ie XRCC5, was subjected to gene-targeted functional genetic analysis in an invertebrate model of AD (Scholz, 2009). Homologs of XRCC5 exist across a wide range of organisms (Altenhoff et al, 2013;Li et al, 2006).…”

Section: Drosophila Studymentioning

confidence: 99%

“…The most convincing finding, XRCC5, was followed up in a functional genetic analysis of its homolog in the fruit fly Drosophila melanogaster. The phenotype alcohol sensitivity (Scholz, 2009) was investigated, as this Drosophila phenotype corresponds to the human phenotype 'level of response'. The level of response to alcohol refers to the psychological and physiological response of an individual to an alcohol challenge.…”

Section: Introductionmentioning

confidence: 99%

XRCC5 as a Risk Gene for Alcohol Dependence: Evidence from a Genome-Wide Gene-Set-Based Analysis and Follow-up Studies in Drosophila and Humans

Juraeva

Treutlein

Scholz

et al. 2014

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

Genetic factors have as large role as environmental factors in the etiology of alcohol dependence (AD). Although genome-wide association studies (GWAS) enable systematic searches for loci not hitherto implicated in the etiology of AD, many true findings may be missed owing to correction for multiple testing. The aim of the present study was to circumvent this limitation by searching for biological system-level differences, and then following up these findings in humans and animals. Gene-set-based analysis of GWAS data from 1333 cases and 2168 controls identified 19 significantly associated gene-sets, of which 5 could be replicated in an independent sample. Clustered in these gene-sets were novel and previously identified susceptibility genes. The most frequently present gene, ie in 6 out of 19 gene-sets, was X-ray repair complementing defective repair in Chinese hamster cells 5 (XRCC5). Previous human and animal studies have implicated XRCC5 in alcohol sensitivity. This phenotype is inversely correlated with the development of AD, presumably as more alcohol is required to achieve the desired effects. In the present study, the functional role of XRCC5 in AD was further validated in animals and humans. Drosophila mutants with reduced function of Ku80-the homolog of mammalian XRCC5-due to RNAi silencing showed reduced sensitivity to ethanol. In humans with free access to intravenous ethanol self-administration in the laboratory, the maximum achieved blood alcohol concentration was influenced in an allele-dose-dependent manner by genetic variation in XRCC5. In conclusion, our convergent approach identified new candidates and generated independent evidence for the involvement of XRCC5 in alcohol dependence.

show abstract

Intoxicated Fly Brains: Neurons Mediating Ethanol-Induced Behaviors

Cited by 18 publications

References 65 publications

The FlyBar: Administering Alcohol to Flies

The FlyBar: Administering Alcohol to Flies

Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish?

XRCC5 as a Risk Gene for Alcohol Dependence: Evidence from a Genome-Wide Gene-Set-Based Analysis and Follow-up Studies in Drosophila and Humans

Contact Info

Product

Resources

About