Chronic itch is a debilitating condition that affects a large portion of the population. It is a symptom of many illnesses including cancer, kidney failure, liver cirrhosis, MS, and shingles. Finding treatments for chronic itch would greatly improve many peoples’ lives. The first step in developing effective treatments is to determine the cellular and molecular mechanisms responsible for itch. Using the zebrafish (Danio rerio) model system, we are exploring whether zebrafish experience pruritus as a discrete sensation from nociception and whether the itch transduction pathways identified in mammals are present in zebrafish. We expect that the advantages of the zebrafish model system, including rapid genetic manipulation, in vivo calcium imaging, and high throughput behavioral screening, will allow us to expand our knowledge of the cellular and molecular mechanisms that allow for the separation of nociception and this novel sensation. The Dhaka Lab is interested in determining what forms of itch, if any, exist in zebrafish so that we may leverage the advantages of the zebrafish model system to characterize the properties of itch stimuli transduction, thus expanding our knowledge of itch pathways and potentially gaining insight into the evolutionary origin of itch in vertebrates. We have been exploring whether compounds that induce itch in mammals, such as agonists of histamine receptor 1, protease-activated receptor 2, and toll like receptor 7, evoke a behavioral and somatosensory response in zebrafish. Our behavioral data shows that imiquimod produces both locomotive behavior in larval zebrafish and a novel lip rubbing behavior in adult zebrafish. Additionally when fish were exposed to imiquimod we observed activity in neurons of the trigeminal ganglion, an exclusively somatosensory cluster of neurons, which indicates that this compound elicits a somatosensory response in zebrafish. We plan to continue characterizing these pathways to increase our understanding of itch, which may aid in the development of novel therapies to treat itch.