Zebrafish make good Guinea Pigs

Pic: Morph of Zebra and Tree Frog


Zebrafish need Prozac like they need a bicycle, yet recording how various molecules affect their behaviour may be the perfect way to discover treatments for mental illness and neurological diseases.

Most brain drugs are variations on 50-year-old medicines, says Randall Peterson of Massachusetts General Hospital in Boston, so new ones can't come soon enough.

Because zebrafish have a similar brain chemistry to humans, how they respond to certain drugs might indicate how the same drugs will affect people.

To investigate, Peterson's team exposed zebrafish embryos to thousands of drugs and recorded how each affected their reaction to a flash of light or a slight poke (Nature Chemical Biology, DOI: 10.1038/nchembio.307). Meanwhile, Alexander Schier at the University of Harvard and colleagues measured how various drugs changed the sleep-wake cycles of zebrafish larvae (Science, DOI: 10.1126/science.1183090]).

Both teams found that each drug had its own "fingerprint" in terms of what kinds of behaviour it produced. And drugs with similar fingerprints tended to tweak the same molecular pathways, which suggests zebrafish behaviour is a good indicator for how a drug will change chemistry in the human brain . "I can't tell you what a psychotic zebrafish looks like but I can tell you what a zebrafish treated with an antipsychotic looks like," says Peterson.

Using this approach, the teams identified chemicals that might treat depression, Alzheimer's disease and sleeping disorders.