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Nat Chem Biol DOI:10.1038/nchembio.307

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

Publication TypeJournal Article
Year of Publication2010
AuthorsKokel, D, Bryan, J, Laggner, C, White, R, Cheung, CYan J, Mateus, R, Healey, D, Kim, S, Werdich, AA, Haggarty, SJ, MacRae, CA, Shoichet, B, Peterson, RT
JournalNat Chem Biol
Date Published2010 Mar

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.


Alternate JournalNat. Chem. Biol.
PubMed ID20081854
PubMed Central IDPMC2834185
Grant ListR21 MH085205-01A1 / MH / NIMH NIH HHS / United States
U01 NS063733 / NS / NINDS NIH HHS / United States
R21 MH085205 / MH / NIMH NIH HHS / United States
R01 GM071896 / GM / NIGMS NIH HHS / United States
R01 MH086867-01 / MH / NIMH NIH HHS / United States
K01 MH091449 / MH / NIMH NIH HHS / United States
T32 HL007208 / HL / NHLBI NIH HHS / United States
U01 NS063733-01 / NS / NINDS NIH HHS / United States
R01 MH086867 / MH / NIMH NIH HHS / United States