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Drosophila melanogaster as a model to study drug addiction.

Kaun KR, Devineni AV, Heberlein U - Hum. Genet. (2012)

Bottom Line: Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties.In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies.Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, University of California-San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.

ABSTRACT
Animal studies have been instrumental in providing knowledge about the molecular and neural mechanisms underlying drug addiction. Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties. In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies. Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction.

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Assays to measure alcohol-induced behavior in Drosophila. a The inebriometer measures ethanol-induced loss of postural control by measuring the time required for flies to fall down the mesh baffles from the top to the bottom of the column (Weber 1988; Moore et al. 1998). b The booz-o-mat allows for the measurement of ethanol-induced hyperactivity and sedation while streaming vaporized ethanol into horizontal tubes containing groups of flies. Hyperactivity is measured by filming the flies and using tracking software to calculate their locomotor speed. Sedation is measured by recording the time required for flies to exhibit the loss-of-righting reflex (Wolf et al. 2002). c The two-choice CAFE assay measures consumption preference for food containing ethanol compared to normal food (Ja et al. 2007; Devineni and Heberlein 2009). d Conditioned ethanol preference is measured by training the flies in a sealed container to associate a neutral odor with the presence of an intoxicating dose of ethanol, and later testing preference for that odor in the absence of ethanol using a Y-maze (Kaun et al. 2011)
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Fig2: Assays to measure alcohol-induced behavior in Drosophila. a The inebriometer measures ethanol-induced loss of postural control by measuring the time required for flies to fall down the mesh baffles from the top to the bottom of the column (Weber 1988; Moore et al. 1998). b The booz-o-mat allows for the measurement of ethanol-induced hyperactivity and sedation while streaming vaporized ethanol into horizontal tubes containing groups of flies. Hyperactivity is measured by filming the flies and using tracking software to calculate their locomotor speed. Sedation is measured by recording the time required for flies to exhibit the loss-of-righting reflex (Wolf et al. 2002). c The two-choice CAFE assay measures consumption preference for food containing ethanol compared to normal food (Ja et al. 2007; Devineni and Heberlein 2009). d Conditioned ethanol preference is measured by training the flies in a sealed container to associate a neutral odor with the presence of an intoxicating dose of ethanol, and later testing preference for that odor in the absence of ethanol using a Y-maze (Kaun et al. 2011)

Mentions: In contrast, high concentrations of ethanol elicit loss of postural control and eventually sedation (Moore et al. 1998; Rothenfluh et al. 2006; Corl et al. 2009). Loss of postural control was initially assayed in the inebriometer, a vertical column containing mesh baffles (Weber 1988; Cohan and Graf 1985; Moore et al. 1998; Fig. 2a). Flies naturally exhibit negative geotaxis and therefore tend to remain at the top of the column, but as they lose postural control they gradually fall from one baffle to the next. Ethanol sensitivity can therefore be measured as the time required for the flies to reach the bottom of the column. Negative geotaxis has also been directly assayed as a measure of ethanol sensitivity by quantifying the vertical distance that flies climb after being knocked to the bottom of a vial (Bhandari et al. 2009). More recently, ethanol-induced loss of postural control (referred to more simply as “sedation”) has been assayed manually using a loss-of-righting reflex assay, in which one counts the number of flies that fail to regain upright posture after being knocked over (Fig. 2b) (Rothenfluh et al. 2006; Corl et al. 2009).Fig. 2


Drosophila melanogaster as a model to study drug addiction.

Kaun KR, Devineni AV, Heberlein U - Hum. Genet. (2012)

Assays to measure alcohol-induced behavior in Drosophila. a The inebriometer measures ethanol-induced loss of postural control by measuring the time required for flies to fall down the mesh baffles from the top to the bottom of the column (Weber 1988; Moore et al. 1998). b The booz-o-mat allows for the measurement of ethanol-induced hyperactivity and sedation while streaming vaporized ethanol into horizontal tubes containing groups of flies. Hyperactivity is measured by filming the flies and using tracking software to calculate their locomotor speed. Sedation is measured by recording the time required for flies to exhibit the loss-of-righting reflex (Wolf et al. 2002). c The two-choice CAFE assay measures consumption preference for food containing ethanol compared to normal food (Ja et al. 2007; Devineni and Heberlein 2009). d Conditioned ethanol preference is measured by training the flies in a sealed container to associate a neutral odor with the presence of an intoxicating dose of ethanol, and later testing preference for that odor in the absence of ethanol using a Y-maze (Kaun et al. 2011)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3351628&req=5

Fig2: Assays to measure alcohol-induced behavior in Drosophila. a The inebriometer measures ethanol-induced loss of postural control by measuring the time required for flies to fall down the mesh baffles from the top to the bottom of the column (Weber 1988; Moore et al. 1998). b The booz-o-mat allows for the measurement of ethanol-induced hyperactivity and sedation while streaming vaporized ethanol into horizontal tubes containing groups of flies. Hyperactivity is measured by filming the flies and using tracking software to calculate their locomotor speed. Sedation is measured by recording the time required for flies to exhibit the loss-of-righting reflex (Wolf et al. 2002). c The two-choice CAFE assay measures consumption preference for food containing ethanol compared to normal food (Ja et al. 2007; Devineni and Heberlein 2009). d Conditioned ethanol preference is measured by training the flies in a sealed container to associate a neutral odor with the presence of an intoxicating dose of ethanol, and later testing preference for that odor in the absence of ethanol using a Y-maze (Kaun et al. 2011)
Mentions: In contrast, high concentrations of ethanol elicit loss of postural control and eventually sedation (Moore et al. 1998; Rothenfluh et al. 2006; Corl et al. 2009). Loss of postural control was initially assayed in the inebriometer, a vertical column containing mesh baffles (Weber 1988; Cohan and Graf 1985; Moore et al. 1998; Fig. 2a). Flies naturally exhibit negative geotaxis and therefore tend to remain at the top of the column, but as they lose postural control they gradually fall from one baffle to the next. Ethanol sensitivity can therefore be measured as the time required for the flies to reach the bottom of the column. Negative geotaxis has also been directly assayed as a measure of ethanol sensitivity by quantifying the vertical distance that flies climb after being knocked to the bottom of a vial (Bhandari et al. 2009). More recently, ethanol-induced loss of postural control (referred to more simply as “sedation”) has been assayed manually using a loss-of-righting reflex assay, in which one counts the number of flies that fail to regain upright posture after being knocked over (Fig. 2b) (Rothenfluh et al. 2006; Corl et al. 2009).Fig. 2

Bottom Line: Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties.In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies.Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, University of California-San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.

ABSTRACT
Animal studies have been instrumental in providing knowledge about the molecular and neural mechanisms underlying drug addiction. Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties. In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies. Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction.

Show MeSH
Related in: MedlinePlus