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A Drosophila model for alcohol reward

Nature Neuroscience volume 14, pages 612–619 (2011)Cite this article

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Abstract

The rewarding properties of drugs contribute to the development of abuse and addiction. We developed a new assay for investigating the motivational properties of ethanol in the genetically tractable model Drosophila melanogaster. Flies learned to associate cues with ethanol intoxication and, although transiently aversive, the experience led to a long-lasting attraction for the ethanol-paired cue, implying that intoxication is rewarding. Temporally blocking transmission in dopaminergic neurons revealed that flies require activation of these neurons to express, but not develop, conditioned preference for ethanol-associated cues. Moreover, flies acquired, consolidated and retrieved these rewarding memories using distinct sets of neurons in the mushroom body. Finally, mutations in scabrous, encoding a fibrinogen-related peptide that regulates Notch signaling, disrupted the formation of memories for ethanol reward. Our results thus establish that Drosophila can be useful for understanding the molecular, genetic and neural mechanisms underling the rewarding properties of ethanol.

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Figure 1: Ethanol is both aversive and rewarding to flies.
Figure 2: Pharmacological properties of ethanol induce preference.
Figure 3: Dopamine is required for conditioned preference.
Figure 4: Dopamine is required for expression of ethanol reward.
Figure 5: The mushroom body is required for aversion and preference.
Figure 6: Sequential use of mushroom body neurons.
Figure 7: sca affects memories for ethanol reward.

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Acknowledgements

We thank S. Waddell, J. Levine, M. Sokolowski, A. Barron and members of the Heberlein laboratory for reagents, input and advice, and S. Birman (Developmental Biology Institute of Marseilles-Luminy), F. Wolf (Gallo Institute), S. Sweeney (University of York), K. Kaiser (Glasgow University), N. Baker (Albert Einstein College of Medicine) and the Bloomington Stock Center for flies. Funding was provided by a Heart and Stroke Foundation of Canada Research Fellowship to K.R.K. and the US National Institutes of Health to U.H.

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Authors and Affiliations

  1. Department of Anatomy, University of California, San Francisco, California, USA

    Karla R Kaun, Reza Azanchi, Zaw Maung & Ulrike Heberlein

  2. Department of Biology, University of Virginia, Charlottesville, Virginia, USA

    Jay Hirsh

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  1. Karla R Kaun
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  2. Reza Azanchi
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Contributions

K.R.K. conceived, conducted and interpreted the experiments, performed data analysis, and co-wrote the paper. R.A. assisted with the behavior experiments. Z.M. conducted control experiments. J.H. performed high-performance liquid chromatography experiments. U.H. conceived and interpreted experiments and co-wrote the paper.

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Correspondence to Karla R Kaun or Ulrike Heberlein.

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Kaun, K., Azanchi, R., Maung, Z. et al. A Drosophila model for alcohol reward. Nat Neurosci 14, 612–619 (2011). https://doi.org/10.1038/nn.2805

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