title: Rapid behavior-based identification of neuroactive small molecules in the zebrafish.
abstract: Neuroactive small molecules are indispensable tools for treating mental illnesses and dissecting nervous system function. However, it has been difficult to discover novel neuroactive drugs. Here, we describe a high-throughput, behavior-based approach to neuroactive small molecule discovery in the zebrafish. We used automated screening assays to evaluate thousands of chemical compounds and found that diverse classes of neuroactive molecules caused distinct patterns of behavior. These 'behavioral barcodes' can be used to rapidly identify new psychotropic chemicals and to predict their molecular targets. For example, we identified new acetylcholinesterase and monoamine oxidase inhibitors using phenotypic comparisons and computational techniques. By combining high-throughput screening technologies with behavioral phenotyping in vivo, behavior-based chemical screens can accelerate the pace of neuroactive drug discovery and provide small-molecule tools for understanding vertebrate behavior.
authors.affiliation: [1] Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA. [2] Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kokel
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bryan
authors.forename: Christian
authors.initials: C
authors.lastname: Laggner
authors.forename: Rick
authors.initials: R
authors.lastname: White
authors.forename: Chung Yan J
authors.initials: CY
authors.lastname: Cheung
authors.forename: Rita
authors.initials: R
authors.lastname: Mateus
authors.forename: David
authors.initials: D
authors.lastname: Healey
authors.forename: Sonia
authors.initials: S
authors.lastname: Kim
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Werdich
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Haggarty
authors.forename: Calum A
authors.initials: CA
authors.lastname: Macrae
authors.forename: Brian
authors.initials: B
authors.lastname: Shoichet
authors.forename: Randall T
authors.initials: RT
authors.lastname: Peterson