Fig. 2

McCarroll et al., 2019 - Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation
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Fig. 2

A high-throughput behavioral screen identifies GABAergic compounds. Zebrafish were treated with various compounds and analyzed for anesthetic-related behaviors. a This scatter plot compares phenoscores of individual wells treated with DMSO or etomidate (6.25 μΜ) (Z-factor = 0.7, n = 944 wells). b This contour plot scores each well from the large-scale behavior-based chemical screen (11,679 compounds, 2336 DMSO controls) by its phenoscore (y-axis) and immobilization index (x-axis). Labels indicate regions with 125 hit compounds (green), 44 toxic compounds (red), and the remaining screening compounds and DMSO controls (blue and gray, respectively). c Structural clustering of the top 125 hit compounds (y-axis) forms 14 clusters using a Tanimoto similarity metric (x-axis). d Example structures of selected compounds in the indicated clusters. e This scatter plot shows a 80.7% reproducibility rate for 57 primary hit compounds. Each point represents the average phenoscore of n = 12 wells at the indicated concentrations (colorbar). The first column represents DMSO controls; the order of other compounds are listed in Supplementary Table 4. f Human GABAAR activation (y-axis) was measured by FLIPR analysis. Of 47 hit compounds, 23 potentiated GABAARs. Compounds 7013338 and 5942595 potentiated GABAARs significantly greater than positive controls (red asterisk = 7013338, two red asterisks = 5942595, P< 0.0001, two-tailed t-test, n = 2–4 replicates as indicated). The hit threshold was defined as 2× the average DMSO control group. Picrotoxin, BGC 20-761, progesterone, and DMSO were used as negative controls (x-axis) while etomidate, tracazolate, propofol, diazepam, and thiopental were used as positive controls. Arrows indicate compounds that were predicted by SEA to bind GABAARs (red arrows) and compounds that bound to TSPO in vitro (green arrowheads)

Expression Data

Expression Detail
Antibody Labeling
Phenotype Data

Phenotype Detail
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