Serotonin and neuropeptide F have opposite modulatory effects on fly aggression


Both serotonin (5-HT) and neuropeptide Y have been shown to affect a variety of mammalian behaviors1,2,3, including aggression4,5. Here we show in Drosophila melanogaster that both 5-HT and neuropeptide F, the invertebrate homolog of neuropeptide Y, modulate aggression. We show that drug-induced increases of 5-HT in the fly brain increase aggression. Elevating 5-HT genetically in the serotonergic circuits recapitulates these pharmacological effects, whereas genetic silencing of these circuits makes the flies behaviorally unresponsive to the drug-induced increase of 5-HT but leaves them capable of aggression. Genetic silencing of the neuropeptide F (npf) circuit also increases fly aggression, demonstrating an opposite modulation to 5-HT. Moreover, this neuropeptide F effect seems to be independent of 5-HT. The implication of these two modulatory systems in fly and mouse aggression suggest a marked degree of conservation and a deep molecular root for this behavior.

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Figure 1: Fighting frequency and pharmacological manipulation of 5-HT levels in fly heads from generation 38.
Figure 2: 5-HTP increases aggression in a linear manner in the selected lines.
Figure 3: Genetic elevation of 5-HT increases aggression, and genetic silencing of the 5-HT circuit makes flies unresponsive to 5-HTP.
Figure 4: Genetic silencing of the npf circuit increases aggression independently of 5-HTP–induced aggression.


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We thank J. Sullivan for help with behavioral analysis, D. Robinson for technical assistance, R. Johnson for 5-HT analysis by HPLC and B. van Swinderen, R. Andretic and S. Pangas for comments on the manuscript. We also thank P. Shen (University of Georgia) for the npf-GAL4 stock and T. Stone (University of California, San Diego) for generating the UAS-dTrh transformants. Ddc-GAL4/TM3, Ser and Th-GAL4/TM3, Ser were provided by J. Hirsch (University of Virginia). UAS-TNT was provided by U. Heberlein (University of San Francisco). This material is based on work supported by the US National Science Foundation under grant number 0432063 (R.J.G. and H.A.D.). R.J.G. is the Dorothy and Lewis B. Cullman Fellow at The Neurosciences Institute, which is supported by the Neurosciences Research Foundation.

Author information




This study was designed by H.A.D. and R.J.G. H.A.D. performed the experiments, analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Herman A Dierick.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Escalating flies and aggression measurement. (PDF 56 kb)

Supplementary Fig. 2

Schematic of 5-HT synthesis. (PDF 22 kb)

Supplementary Fig. 3

Linear regression plot of fighting frequencies of treated and untreated lines. (PDF 28 kb)

Supplementary Table 1

Gene products involved in 5-HT function and their mammalian homologs. (PDF 14 kb)

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Dierick, H., Greenspan, R. Serotonin and neuropeptide F have opposite modulatory effects on fly aggression. Nat Genet 39, 678–682 (2007).

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