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A Drosophila model for alcohol reward

Nature Neuroscience volume 14, pages 612619 (2011) | Download Citation

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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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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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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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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Karla R Kaun or Ulrike Heberlein.

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DOI

https://doi.org/10.1038/nn.2805

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