Identification of zebrafish histamine H1, H2 and H3 receptors and effects of histaminergic ligands on behavior

Neuronal histamine regulates several functions in the vertebrate brain. The zebrafish brain contains a widespread histaminergic system and H3 receptor ligand binding has been reported. In this study we provide evidence for the existence of histamine H1, H2 and H3 receptor genes in zebrafish. Single copies of putative histamine H1, H2 and H3 receptors were identified and cloned from the zebrafish brain. Expression analysis suggested that they are expressed in the brain and a few other tissues. Widespread distribution of zebrafish H2 receptor binding sites was detected with [125I]iodoaminopotentidine in brain sections. Zebrafish larvae were exposed to 1, 10 or 100 μM of the H1 ligand pyrilamine, the H2 ligand cimetidine and the H3 ligands thioperamide and immepip for 5 days. Significant decreases in swimming distance were observed with the highest dose of all ligands, whereas cimetidine gave a significant decrease also with 1 and 10 μM doses. These results provide the first molecular biological evidence for the presence of histamine receptors in zebrafish. These histamine receptors resemble those of higher vertebrates and they provide a useful model for pharmacological and behavioral studies for characterizing the functions of histamine in more detail.