title: Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.
abstract: Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action on the basis of behavioral profiles alone. Although zebrafish (Danio rerio) behavior has been used to rapidly identify neuroactive compounds, it is not clear what types of behavioral assays would be necessary to identify multitarget compounds such as antipsychotics. Here we developed a battery of behavioral assays in larval zebrafish to determine whether behavioral profiles can provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated zebrafish could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multitarget mechanisms of action.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.|Teleos Therapeutics, Medford, Massachusetts, USA.
authors.forename: Giancarlo
authors.identifier: 0000-0003-2850-4633
authors.initials: G
authors.lastname: Bruni
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.|Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Charlestown, Massachusetts, USA.|Department of Systems Biology, Harvard Medical School, Charlestown, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Andrew J
authors.identifier: 0000-0001-6174-7253
authors.initials: AJ
authors.lastname: Rennekamp
authors.affiliation: Teleos Therapeutics, Medford, Massachusetts, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Velenich
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California, USA.|Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: McCarroll
authors.affiliation: Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.|Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Gendelev
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California, USA.|Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Fertsch
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California, USA.|Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California, USA.|Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Parth
authors.initials: P
authors.lastname: Lakhani
authors.affiliation: Teleos Therapeutics, Medford, Massachusetts, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Lensen
authors.affiliation: Teleos Therapeutics, Medford, Massachusetts, USA.
authors.forename: Tama
authors.initials: T
authors.lastname: Evron
authors.affiliation: NeuroBehavior Laboratory, Harvard NeuroDiscovery Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lorello
authors.affiliation: Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA.|NIMH Psychoactive Drug Screening Program, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA.
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Huang
authors.affiliation: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kolczewski
authors.affiliation: Teleos Therapeutics, Medford, Massachusetts, USA.
authors.forename: Galen
authors.initials: G
authors.lastname: Carey
authors.affiliation: NeuroBehavior Laboratory, Harvard NeuroDiscovery Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Caldarone
authors.affiliation: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Prinssen
authors.affiliation: Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA.|NIMH Psychoactive Drug Screening Program, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.affiliation: Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.|Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Michael J
authors.identifier: 0000-0002-1240-2192
authors.initials: MJ
authors.lastname: Keiser
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.|Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Charlestown, Massachusetts, USA.|Department of Systems Biology, Harvard Medical School, Charlestown, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Randall T
authors.initials: RT
authors.lastname: Peterson
authors.affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California, USA.|Institute for Neurodegenerative Disease, University of California, San Francisco, San Francisco, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kokel
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D007814:Larva / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D015027:Zebrafish / Q000254:growth & development
chemical_list: D014150:Antipsychotic Agents