Leveraging Large-scale Behavioral Profiling in Zebrafish to Explore Neuroactive Polypharmacology

Abstract

Many psychiatric drugs modulate the nervous system through multitarget mechanisms. However, systematic identification of multitarget compounds has been difficult using traditional in vitro screening assays. New approaches to phenotypic profiling in zebrafish can help researchers identify novel compounds with complex polypharmacology. For example, large-scale behavior-based chemical screens can rapidly identify large numbers of structurally diverse and phenotype-related compounds. Once these compounds have been identified, a systems-level analysis of their structures may help to identify statistically enriched target pathways. Together, systematic behavioral profiling and multitarget predictions may help researchers identify new behavior-modifying pathways and CNS therapeutics.