Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 2,292

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target

Open access
Gasque, Gabriel, Conway, Stephen, Huang, Juan, Rao, Yi, Vosshall, Leslie B.·2013·Scientific Reports
DOI 10.1038/srep02120
Open this paper in CoChat — free account

Abstract

Dysregulation of eating behavior can lead to obesity, which affects 10% of the adult population worldwide and accounts for nearly 3 million deaths every year. Despite this burden on society, we currently lack effective pharmacological treatment options to regulate appetite. We used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake. In a screen of 3630 small molecules, we identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug. Using cell-based assays we show that metitepine is an antagonist of all five Drosophila 5-HT receptors. We screened fly mutants for each of these receptors and found that serotonin receptor 5-HT2A is the sole molecular target for feeding inhibition by metitepine. These results highlight the conservation of molecular mechanisms controlling appetite and provide a method for unbiased whole-organism drug screens to identify novel drugs and molecular pathways modulating food intake.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/srep02120

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 2 references

Research works printed but not linked: 39

  1. Dietrich, M. O. & Horvath, T. L. Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons. Nat. Rev. Drug. Discov. 11, 675–691 (2012). · DOI · Paper page
  2. Huntington, M. K. & Shewmake, R. A. Anti-obesity drugs: are they worth it? Future. Med. Chem. 3, 267–269 (2011). · DOI
  3. Oury, F. & Karsenty, G. Towards a serotonin-dependent leptin roadmap in the brain. Trends Endocrinol. Metab. 22, 382–387 (2011). · DOI
  4. Broberger, C. Brain regulation of food intake and appetite: molecules and networks. J. Intern. Med. 258, 301–327 (2005). · DOI · Paper page
  5. Yeo, G. S. & Heisler, L. K. Unraveling the brain regulation of appetite: lessons from genetics. Nat. Neurosc. i 15, 1343–1349 (2012). · DOI · Paper page
  6. Rihel, J. et al. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327, 348–351 (2010). · DOI · Paper page
  7. Petrascheck, M., Ye, X. & Buck, L. B. An antidepressant that extends lifespan in adult Caenorhabditis elegans. Nature 450, 553–556 (2007). · DOI · Paper page
  8. Dar, A. C., Das, T. K., Shokat, K. M. & Cagan, R. L. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature 486, 80–84 (2012). · DOI · Paper page
  9. Chang, S. et al. Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat. Chem. Biol. 4, 256–263 (2008). · DOI · Paper page
  10. Bland, M. L., Lee, R. J., Magallanes, J. M., Foskett, J. K. & Birnbaum, M. J. AMPK supports growth in Drosophila by regulating muscle activity and nutrient uptake in the gut. Dev. Biol. 344, 293–303 (2010). · DOI
  11. Gutierrez, E., Wiggins, D., Fielding, B. & Gould, A. P. Specialized hepatocyte-like cells regulate Drosophila lipid metabolism. Nature 445, 275–280 (2007). · DOI · Paper page
  12. Rajan, A. & Perrimon, N. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell 151, 123–137 (2012). · DOI · Paper page
  13. Rulifson, E. J., Kim, S. K. & Nusse, R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296, 1118–1120 (2002). · DOI · Paper page
  14. Kim, S. K. & Rulifson, E. J. Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells. Nature 431, 316–320 (2004). · DOI · Paper page
  15. Rusten, T. E. et al. Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathway. Dev. Cell. 7, 179–192 (2004). · DOI · Paper page
  16. Scott, R. C., Schuldiner, O. & Neufeld, T. P. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev. Cell. 7, 167–178 (2004). · DOI · Paper page
  17. Carvalho, G. B., Kapahi, P. & Benzer, S. Compensatory ingestion upon dietary restriction in Drosophila melanogaster. Nat. Methods 2, 813–815 (2005). · DOI · Paper page
  18. Musselman, L. P. et al. A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. Dis. Model. Mech. 4, 842–849 (2011). · DOI · Paper page
  19. Melcher, C. & Pankratz, M. J. Candidate gustatory interneurons modulating feeding behavior in the Drosophila brain. PLoS Biol. 3, e305 (2005). · DOI · Paper page
  20. Zinke, I., Kirchner, C., Chao, L. C., Tetzlaff, M. T. & Pankratz, M. J. Suppression of food intake and growth by amino acids in Drosophila: the role of pumpless, a fat body expressed gene with homology to vertebrate glycine cleavage system. Development 126, 5275–5284 (1999). · DOI
  21. Tokunaga, T., Noburu, T. & Ueda, M. Mechanism of antifeedant activity of plumbagin, a compound concerning the chemical defense in carnivorous plant. Tetrahedron Lett. 45, 7115–7119 (2004). · doi:10.1016/j.tetlet.2004.07.094
  22. Kubo, I. & Klocke, J. A. Some terpenoid insect antifeedants from tropical sources. Adv. Pestic. Sci. 2, 284–291 (1986).
  23. Simon, A. F. et al. Drosophila vesicular monoamine transporter mutants can adapt to reduced or eliminated vesicular stores of dopamine and serotonin. Genetics 181, 525–541 (2009). · DOI
  24. Saudou, F., Boschert, U., Amlaiky, N., Plassat, J. L. & Hen, R. A family of Drosophila serotonin receptors with distinct intracellular signalling properties and expression patterns. EMBO J. 11, 7–17 (1992). · DOI · Paper page
  25. Colas, J. F., Launay, J. M., Kellermann, O., Rosay, P. & Maroteaux, L. Drosophila 5-HT2 serotonin receptor: coexpression with fushi-tarazu during segmentation. Proc. Natl. Acad. Sci. U. S. A. 92, 5441–5445 (1995). · DOI · Paper page
  26. Witz, P. et al. Cloning and characterization of a Drosophila serotonin receptor that activates adenylate cyclase. Proc. Natl. Acad. Sci. U. S. A. 87, 8940–8944 (1990). · DOI · Paper page
  27. Obosi, L. A. et al. Functional characterisation of the Drosophila 5-HTdro1 and 5-HTdro2B serotonin receptors in insect cells: activation of a G(alpha) s-like protein by 5-HTdro1 but lack of coupling to inhibitory G-proteins by 5-HTdro2B. FEBS Lett. 381, 233–236 (1996). · DOI
  28. Hauser, F., Cazzamali, G., Williamson, M., Blenau, W. & Grimmelikhuijzen, C. J. A review of neurohormone GPCRs present in the fruitfly Drosophila melanogaster and the honey bee Apis mellifera. Prog. Neurobiol. 80, 1–19 (2006). · DOI · Paper page
  29. Yuan, Q., Joiner, W. J. & Sehgal, A. A sleep-promoting role for the Drosophila serotonin receptor 1A. Curr. Biol. 16, 1051–1062 (2006). · DOI · Paper page
  30. Nichols, C. D. 5-HT2 receptors in Drosophila are expressed in the brain and modulate aspects of circadian behaviors. Dev. Neurobiol. 67, 752–763 (2007). · DOI
  31. Osterwalder, T., Yoon, K. S., White, B. H. & Keshishian, H. A conditional tissue-specific transgene expression system using inducible GAL4. Proc. Natl. Acad. Sci. U. S. A. 98, 12596–12601 (2001). · DOI · Paper page
  32. Song, B. M. & Avery, L. Serotonin activates overall feeding by activating two separate neural pathways in Caenorhabditis elegans. J. Neurosci. 32, 1920–1931 (2012). · DOI
  33. Neckameyer, W. S. A trophic role for serotonin in the development of a simple feeding circuit. Dev. Neurosci. 32, 217–237 (2010). · DOI
  34. Vargas, M. A., Luo, N., Yamaguchi, A. & Kapahi, P. A role for S6 kinase and serotonin in postmating dietary switch and balance of nutrients in D. melanogaster. Curr. Biol. 20, 1006–1011 (2010). · DOI · Paper page
  35. Mair, W. & Dillin, A. Aging and survival: the genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 77, 727–754 (2008). · DOI · Paper page
  36. Lam, D. D., Garfield, A. S., Marston, O. J., Shaw, J. & Heisler, L. K. Brain serotonin system in the coordination of food intake and body weight. Pharmacol. Biochem. Behav. 97, 84–91 (2010). · DOI · Paper page
  37. Bier, E. Drosophila, the golden bug, emerges as a tool for human genetics. Nat. Rev. Genet. 6, 9–23 (2005). · DOI · Paper page
  38. Offermanns, S. & Simon, M. I. G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C. J. Biol. Chem. 270, 15175–15180 (1995). · DOI · Paper page
  39. Metaxakis, A., Oehler, S., Klinakis, A. & Savakis, C. Minos as a genetic and genomic tool in Drosophila melanogaster. Genetics 171, 571–581 (2005). · DOI · Paper page

Cited by

See all 2,292

Metadata

Authors
Gasque, G., Conway, S., Huang, J., Rao, Y., & Vosshall, L. B.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2013-07-02
Volume
3
Issue
1
Pages
srep02120-srep02120
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep02120
OpenAlex
W2060870711
Cited by
2,292
References
2
FWCI
118.83
Type
journal article
Language
en
Open access
gold
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target. https://app.cochat.ai/papers/10.1038/srep02120
The paper
Gasque, G., Conway, S., Huang, J., Rao, Y., & Vosshall, L. B. (2013). Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target. Scientific Reports. https://doi.org/10.1038/srep02120

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.