# Behavioral Profiling in Zebrafish Identifies Insecticide-Related Compounds

## TL;DR

Researchers used zebrafish behavior to find new insecticides that target GABA receptors, leading to potential pest control solutions.

## Contribution

A novel behavior-based screening method in zebrafish to identify GABA receptor-targeting insecticides.

## Key findings

- Endosulfan increased zebrafish motor activity under specific light stimuli, indicating a unique behavioral response.
- Screening 9,000 compounds identified several that phenocopied endosulfan's effects in zebrafish.
- One identified compound showed insecticidal activity against the Western corn rootworm in vivo.

## Abstract

Pesticides, including
insecticides, are indispensable for large-scale
agriculture. Modulating chloride ion channels has proven highly successful
as a mode of action (MoA) for insect management. Identifying new ligands
for these channels affords opportunities for the potential development
of new insecticide products. We discovered an unexpected behavioral
response in larval zebrafish exposed to endosulfan, a γ-aminobutyric
acid (GABA)-gated chloride channel modulator. At low concentrations,
endosulfan increased zebrafish motor activity under strobing blue
or green light stimuli. Using this distinct behavioral phenotype as
a proxy for similar modes of action, we screened over 9,000 compounds
and identified several structurally diverse hits that phenocopied
endosulfan’s effects in vivo. Nine selected
hits were tested in an in vitro GABA receptor (GABAR)
oocyte assay, confirming that certain compounds block Drosophila GABAR
activation. Subsequent in vivo insect assays revealed
that one of these GABAR antagonists showed insecticidal activity against
the Western corn rootworm (Diabrotica virgifera virgifera), which is a commercially important pest of corn. Our findings demonstrate
a new approach for identifying GABAR-targeting insecticides through
behavior-based screening in zebrafish.