Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.

Nat Chem Biol
Authors
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.

Year of Publication
2016
Journal
Nat Chem Biol
Volume
12
Issue
7
Pages
559-66
Date Published
2016 Jul
ISSN
1552-4469
URL
DOI
10.1038/nchembio.2097
PubMed ID
27239787
PubMed Central ID
PMC4912417
Links
Grant list
R21 MH085205 / MH / NIMH NIH HHS / United States
T32 GM008284 / GM / NIGMS NIH HHS / United States
K01 MH091449 / MH / NIMH NIH HHS / United States
R44 GM093456 / GM / NIGMS NIH HHS / United States
T32 EB009383 / EB / NIBIB NIH HHS / United States
U01 MH105027 / MH / NIMH NIH HHS / United States
T32 HL007208 / HL / NHLBI NIH HHS / United States
R01 MH086867 / MH / NIMH NIH HHS / United States
R01 AA022583 / AA / NIAAA NIH HHS / United States