rapid behavior-based identification of neuroactive small molecules in the zebrafish

Published: 01-17-2010 In Publication


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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.