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Rapid behavior-based identification of neuroactive small molecules in the zebrafish.

Publication TypeJournal Article
AuthorsKokel, D., Bryan J., Laggner C., White R., Cheung CY, Mateus R., Healey D., Kim S., Werdich AA, Haggarty SJ, Macrae CA, Shoichet B., and Peterson RT
AbstractNeuroactive 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.
Year of Publication2010
JournalNature chemical biology
Volume6
Issue3
Pages231-237
Date Published (YYYY/MM/DD)2010/03/01
ISSN Number1552-4450
DOI10.1038/nchembio.307
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/20081854?dopt=Abstract