Identification of zebrafish histamine H, H and H 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 H-3 receptor ligand binding has been reported. In this study we provide evidence for the existence of histamine H-1, H-2 and H-3 receptor genes in zebrafish. Single copies of putative histamine H-1, H-2 and H-3 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 [I-125]iodoaminopotentidine in brain sections. Zebrafish larvae were exposed to 1, 10 or 100 mu M of the H-1 ligand pyrilamine, the H-2 ligand cimetidine and the H-3 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 mu M 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. (c) 2007 Elsevier Inc. All rights reserved.