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Insulin signaling regulates lifespan, reproduction, metabolic homeostasis, and resistance to stress in the adult organism. In Drosophila, there are seven insulin-like peptides (DILP1–7). Three of these (DILP2, 3 and 5) are produced in median neurosecretory cells of the brain, designated IPCs. Previous work has suggested that production or release of DILPs in IPCs can be regulated by a factor secreted from the fat body as well as by neuronal GABA or short neuropeptide F. There is also evidence that serotonergic neurons may regulate IPCs. Here, we investigated mechanisms by which serotonin may regulate the IPCs. We show that the IPCs in adult flies express the 5-HT_1A, but not the 5-HT_1B or 5-HT₇ receptors, and that processes of serotonergic neurons impinge on the IPC branches. Knockdown of 5-HT_1A in IPCs by targeted RNA interference (RNAi) leads to increased sensitivity to heat, prolonged …