Insulin signaling in the nervous system regulates ethanol intoxication in Drosophila melanogaster

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The insulin signaling pathway regulates multiple physiological processes, including energy metabolism, organismal growth, aging and reproduction. Here we show that genetic manipulations in Drosophila melanogaster that impair the function of insulin-producing cells or of the insulin-receptor signaling pathway in the nervous system lead to increased sensitivity to the intoxicating effects of ethanol. These findings suggest a previously unknown role for this highly conserved pathway in regulating the behavioral responses to an addictive drug.

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Figure 1: PKA inhibition in IPCs results in increased ethanol sensitivity.
Figure 2: Mutations in the InR and CHICO cause increased ethanol sensitivity.
Figure 3: Perturbation of insulin signaling in the nervous system alters ethanol sensitivity.


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We thank E. Rulifson, M. Jünger and E. Hafen for providing fly strains prior to publication. This work was supported by US National Institutes of Health grants AA10035 and AA13105, and by the McKnight Foundation for Neuroscience.

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Correspondence to Ulrike Heberlein.

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The authors declare no competing financial interests.

Supplementary information

Supplemantary Fig. 1

Inhibition of PKA in IPCs does not cause alterations in ethanol pharmacokinetics. Ethanol levels were measured in extracts of flies of the indicated genotypes (see Supplementary Methods for details). Ethanol exposure is continuous starting at time = 0. (JPG 60 kb)

(n = 3 for all genotypes.) One-way ANOVA across each time point, with the critical p value adjusted to α = 0.01, did not reveal significant differences between the genotypes at any of the five time points (P > 0.05).

Supplemantary Methods (PDF 39 kb)

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Corl, A., Rodan, A. & Heberlein, U. Insulin signaling in the nervous system regulates ethanol intoxication in Drosophila melanogaster. Nat Neurosci 8, 18–19 (2005) doi:10.1038/nn1363

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