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

By Gabriel Gasque, S. Conway, Juan Huang, Y. Rao, Leslie B. Vosshall. Scientific Reports, 2013

652 citations recorded by the source corpus.

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.

Subfields: Aging, Cellular and Molecular Neuroscience, Insect Science

View Paper: https://www.semanticscholar.org/paper/ffe17c4a8be49b4b164617b9e8eaf53b58f908c8

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Citations in the corpus

Cell Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression (2016, neutral): “This difference may highlight other roles these neurons play either in either courtship (Becnel et al., 2011) or feeding and aggression (Gasque et al., 2013; Johnson et al., 2009).”
Serotonin, serotonin receptors and their actions in insects (2014, background): “On the contrary, entrainment of the Drosophila circadian clock to light was inhibited by 5-HT [37].”