A microbial metabolite synergizes with endogenous serotonin to triggerC. elegansreproductive behavior

Significance Neurochemical signaling pathways are important therapeutic targets for the treatment of brain disorders, including complex psychiatric disorders that affect poorly understood cognitive and affective mechanisms. Despite a pressing need for improved psychopharmacology, it has proved difficult to discover new types of small molecules that target neurochemical signaling. We have used a behavior-based screen to identify natural products that strongly and specifically interact with serotonin signaling in the nervous system of the nematode Caenorhabditis elegans . This approach identified a microbial metabolite that is structurally unrelated to known activators of serotonin signaling. Our study suggests that microbe-derived small molecules can be a rich source of novel neuroactive compounds.