Molecular and neural basis of vomiting behavior in <i>Drosophila melanogaster</i>

Vomiting is a common yet poorly understood symptom, largely due to the lack of conventional animal models. This study establishes a <i>Drosophila</i> model for vomiting triggered by berberine ingestion. Our findings reveal that this response is mediated by the chemoreceptor TrpA1, which is indirectly activated by berberine via the mAChRs-PLC pathway. Berberine induces acetylcholine release from foregut epithelial cells, which triggers tachykinin secretion from intestinal tracheal cells. Tachykinins contract the visceral muscles, particularly the P4 pump of the foregut, and suppress myosuppressin release from pars intercerebralis neurons, thereby promoting crop motility. We further demonstrate the conservation of key genes involved in mammalian vomiting regulation. Overall, this study provides a molecular and cellular framework for understanding vomiting and introduces <i>Drosophila</i> as a genetic model for mechanistic studies.