Methods for drug screening efforts during drug discovery are mostly inadequate to address the complexity of interactions within the intact body. These limits become even more apparent when the drugs are meant to target behavior and psychology. A paper published earlier this year (“Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation” January 15, 2010 in Science) presents a promising technique to address these limits.

The team developed a whole organism, high-throughput screen for drugs. They placed individual zebrafish larva into wells with the drug that they wanted to test. Each plate had 80 zebrafish larva moving around in their own wells. Behavior was automatically measured using video recording techniques and automated tracking software. The results went through cluster analysis.

Behavioral profiling results showed:

• relationships between the drugs tested and their targets
• a conserved vertebrate neuropharmacology
• identified regulators of the target behavior

Individual drugs with unknown targets were clustered with drugs with known neuropharmacological properties. The well-known drugs could predict the targets for the drugs without characterized targets that were clustered with them. In addition, behavioral profiling identified previously unidentified pathways involved in the target behavior. I recommend this article to anyone wondering how to get a handle on the huge number of variables that need to be addressed in drug discovery, systems biology, and neuroscience.