Arthropod EFLamide genes in chelicerates, myriapods, decapods and non pterygote hexapods encode various EFLamide paracopies on a single precursor. However, in more advanced insect species such multiple EFLamide paracopies encoding genes are absent. In some Hemiptera putative exons of an EFLamide gene coding for a single EFLamide have been identified, while in the migratory locust a similar exon could potentially code for two EFLamide peptides. The recent identification of an EFLGamide from Platynereis dumerilii as the ligand for an ortholog of the TRH GPCR, suggested that the arthropod EFLamides might similarly activate TRH GPCR orthologs. We here identify the TRH GPCR ortholog from Locusta migratoria and show that it is activated in nanomolar concentrations by the two EFLamides previously predicted from this species. We also show that in the central nervous system there seems to be only a single bilateral neuron in the protocerebrum expressing this peptide. Given this very limited expression of EFLamide in locusts, it is perhaps not surprising that this gene and its receptor have been lost in many other insect species. This shows again that although neuropeptides and their receptors may persist in different evoltionary lineages, their functions can change dramatically.,Copyright © 2019. Published by Elsevier Ltd.