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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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Common genetic tools in Drosophila.a The Gal4/UAS system (Brand and Perrimon 1993). The transcriptional activator Gal4 is expressed in a spatially restricted pattern and activates any gene placed downstream of the upstream activating sequence (UAS). b The TARGET system (McGuire et al. 2003). At the restrictive temperature (30°C), Gal80ts is inactive, Gal4 is active and UAS-driven genes are expressed. At the permissive temperature (19°C), Gal80ts is active, Gal4 is inhibited, and UAS-driven genes are not expressed. c The Shibirets system (Kitamoto 2001). At the restrictive temperature (30°C), but not the permissive temperature (19°C), Shits blocks neurotransmission by disrupting endocytosis and thereby depleting synaptic vesicles. d The TrpA1 system (Hamada et al. 2008; Pulver et al. 2009). At the restrictive temperature (27°C), but not the permissive temperature (19°C), cation flow through the temperature-gated cation channel dTRPA1 causes neuronal depolarization
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Fig1: Common genetic tools in Drosophila.a The Gal4/UAS system (Brand and Perrimon 1993). The transcriptional activator Gal4 is expressed in a spatially restricted pattern and activates any gene placed downstream of the upstream activating sequence (UAS). b The TARGET system (McGuire et al. 2003). At the restrictive temperature (30°C), Gal80ts is inactive, Gal4 is active and UAS-driven genes are expressed. At the permissive temperature (19°C), Gal80ts is active, Gal4 is inhibited, and UAS-driven genes are not expressed. c The Shibirets system (Kitamoto 2001). At the restrictive temperature (30°C), but not the permissive temperature (19°C), Shits blocks neurotransmission by disrupting endocytosis and thereby depleting synaptic vesicles. d The TrpA1 system (Hamada et al. 2008; Pulver et al. 2009). At the restrictive temperature (27°C), but not the permissive temperature (19°C), cation flow through the temperature-gated cation channel dTRPA1 causes neuronal depolarization

Mentions: Some of the genetic tools developed in Drosophila have particular relevance to studying the relationship between genes, the brain, and behavior. For example, genetic tools in flies allow one to manipulate the nervous system independently of other tissues in the body. Furthermore, because different neural circuits may have distinct and perhaps opposing roles in behavior, one would ideally like to target specific sets of neurons within the brain. This cellular specificity can be accomplished by the bipartite Gal4/UAS system, in which the transcriptional activator Gal4 is expressed in a spatially restricted pattern and activates any gene placed downstream of the upstream activating sequence (UAS) (Brand and Perrimon 1993; Fig. 1a). The generation and characterization of thousands of Gal4 lines expressed in various patterns allow for manipulation of specific brain regions or neuronal types (Pfeiffer et al. 2008). This technique allows one to ask in which neurons a particular gene functions to regulate a behavioral response. These patterns can be further spatially refined to very small subsets of neurons using the “split Gal4 system” in which the DNA-binding and transcriptional-activation domains of Gal4 are targeted to different neuronal subsets using different promoters; transcriptional activation of target genes occurs only in neurons expressing both domains (Luan et al. 2006). Temporal specificity can be achieved by using a temperature-sensitive Gal4 repressor called Gal80ts and shifting the flies from the permissive to the restrictive temperature during a particular time period (McGuire et al. 2003; Fig. 1b).Fig. 1


Drosophila melanogaster as a model to study drug addiction.

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

Common genetic tools in Drosophila.a The Gal4/UAS system (Brand and Perrimon 1993). The transcriptional activator Gal4 is expressed in a spatially restricted pattern and activates any gene placed downstream of the upstream activating sequence (UAS). b The TARGET system (McGuire et al. 2003). At the restrictive temperature (30°C), Gal80ts is inactive, Gal4 is active and UAS-driven genes are expressed. At the permissive temperature (19°C), Gal80ts is active, Gal4 is inhibited, and UAS-driven genes are not expressed. c The Shibirets system (Kitamoto 2001). At the restrictive temperature (30°C), but not the permissive temperature (19°C), Shits blocks neurotransmission by disrupting endocytosis and thereby depleting synaptic vesicles. d The TrpA1 system (Hamada et al. 2008; Pulver et al. 2009). At the restrictive temperature (27°C), but not the permissive temperature (19°C), cation flow through the temperature-gated cation channel dTRPA1 causes neuronal depolarization
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3351628&req=5

Fig1: Common genetic tools in Drosophila.a The Gal4/UAS system (Brand and Perrimon 1993). The transcriptional activator Gal4 is expressed in a spatially restricted pattern and activates any gene placed downstream of the upstream activating sequence (UAS). b The TARGET system (McGuire et al. 2003). At the restrictive temperature (30°C), Gal80ts is inactive, Gal4 is active and UAS-driven genes are expressed. At the permissive temperature (19°C), Gal80ts is active, Gal4 is inhibited, and UAS-driven genes are not expressed. c The Shibirets system (Kitamoto 2001). At the restrictive temperature (30°C), but not the permissive temperature (19°C), Shits blocks neurotransmission by disrupting endocytosis and thereby depleting synaptic vesicles. d The TrpA1 system (Hamada et al. 2008; Pulver et al. 2009). At the restrictive temperature (27°C), but not the permissive temperature (19°C), cation flow through the temperature-gated cation channel dTRPA1 causes neuronal depolarization
Mentions: Some of the genetic tools developed in Drosophila have particular relevance to studying the relationship between genes, the brain, and behavior. For example, genetic tools in flies allow one to manipulate the nervous system independently of other tissues in the body. Furthermore, because different neural circuits may have distinct and perhaps opposing roles in behavior, one would ideally like to target specific sets of neurons within the brain. This cellular specificity can be accomplished by the bipartite Gal4/UAS system, in which the transcriptional activator Gal4 is expressed in a spatially restricted pattern and activates any gene placed downstream of the upstream activating sequence (UAS) (Brand and Perrimon 1993; Fig. 1a). The generation and characterization of thousands of Gal4 lines expressed in various patterns allow for manipulation of specific brain regions or neuronal types (Pfeiffer et al. 2008). This technique allows one to ask in which neurons a particular gene functions to regulate a behavioral response. These patterns can be further spatially refined to very small subsets of neurons using the “split Gal4 system” in which the DNA-binding and transcriptional-activation domains of Gal4 are targeted to different neuronal subsets using different promoters; transcriptional activation of target genes occurs only in neurons expressing both domains (Luan et al. 2006). Temporal specificity can be achieved by using a temperature-sensitive Gal4 repressor called Gal80ts and shifting the flies from the permissive to the restrictive temperature during a particular time period (McGuire et al. 2003; Fig. 1b).Fig. 1

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