700 - 800 Mya
||Rut Vleugels, Heleen Verlinden, Jozef Vanden Broeck, Serotonin, serotonin receptors and their actions in insects, Neurotransmitter 2015 2: e314. doi: 10.14800/nt.314 p.3 right column 3rd paragraph
|| Peroutka SJ, Howell TA. The molecular evolution of G protein-coupled receptors: focus on 5-hydroxytryptamine receptors. Neuropharmacology. 1994 Mar-Apr33(3-4):319-24.  Walker RJ, Brooks HL, Holden-Dye L. Evolution and overview of classical transmitter molecules and their receptors. Parasitology 1996 113 Suppl:S3-33.  Tierney AJ. Structure and function of invertebrate 5-HT receptors: a review. Comp Biochem Physiol A 2001 128: 791-804.  Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 2002 71: 533-554.PubMed ID7984268, 9051927, 11282322, 11888546
||P.3 right column 3rd paragraph: "5-HT is one of the oldest signaling molecules in evolution, which may explain why 5-HT interacts with such a diversity of receptors belonging to the G protein-coupled receptor (GPCR) and the ligand-gated ion-channel families. The first 5-HT receptors are estimated to have appeared 700 to 800 million years ago in single-celled eukaryotes, such as paramecia [primary sources]."