title: Using the zebrafish photomotor response for psychotropic drug screening.
abstract: Because psychotropic drugs affect behavior, we can use changes in behavior to discover psychotropic drugs. The original prototypes of most neuroactive medicines were discovered in humans, rodents and other model organisms. Most of these discoveries were made by chance, but the process of behavior based drug discovery can be made more systematic and efficient. Fully automated platforms for analyzing the behavior of embryonic zebrafish capture digital video recordings of animals in each individual well of a 96-well plate before, during, and after a series of stimuli. To analyze systematically the thousands of behavioral recordings obtained from a large-scale chemical screen, we transform these behavioral recordings into numerical barcodes, providing a concise and interpretable summary of the observed phenotypes in each well. Systems-level analysis of these behavioral phenotypes generate testable hypotheses about the molecular mechanisms of poorly understood drugs and behaviors. By combining the in vivo relevance of behavior-based phenotyping with the scale and automation of modern drug screening technologies, systematic behavioral barcoding represents a means of discovering psychotropic drugs and provides a powerful, systematic approach for unraveling the complexities of vertebrate behavior.
authors.affiliation: Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kokel
authors.forename: Randall T
authors.initials: RT
authors.lastname: Peterson
mesh_terms: D000465:Algorithms; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D057205:Automation, Laboratory; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D003623:Dark Adaptation; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D057166:High-Throughput Screening Assays; D006801:Humans; D007259:Infrared Rays; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D010641:Phenotype; D011618:Psychotic Disorders / Q000188:drug therapy; D012107:Research Design; D054852:Small Molecule Libraries / Q000494:pharmacology*; D014741:Video Recording / Q000295:instrumentation / Q000379:methods; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents; D054852:Small Molecule Libraries