A Tropical Fish May Provide Key to Treating Opioid Dependency

By Paul Gaita 08/30/17

Researchers think the zebrafish—which shares 70% of the same genes as humans—could offer real insight into addiction. 

zebra fish

Researchers from the University of Utah may have found a new path to providing treatment for opioid dependency in the most unlikely of sources—the zebrafish, a tiny freshwater relative of the minnow.

Though best known as a popular aquarium pet, the zebrafish is also widely used in scientific research due to its genetic and physiological similarities to people—humans and zebrafish share 70% of genes—and those traits provided researchers with a working model of the biological connection between addiction and withdrawal by conditioning the fish to self-administer opioid doses, and then observe their reactions to symptoms similar to withdrawal. In doing so, the study may provide further clues and possible tests for therapies to arrest drug-seeking behavior in humans.

Though similar tests have been conducted on rodents and primates, zebrafish may be the most ideal subject for such research, due not only to their shared genetic traits, but also to a similar system in their brains which trigger production of the reward neurotransmitters dopamine and glutamate in a manner similar to humans. Those elements proved crucial to the researchers' study, which began with conditioning the fish to trigger the release of food in a tank equipped with a motion sensor. When the fish crossed the tank, the sensor released the food into the water and signaled its release with a green light. The fish soon discovered that they could get food at any time by crossing the tank.

Researchers then replaced the food with hydrocodone and repeated the set-up involving the motion sensor, but added a continuous flow of water to the tank, which forced the fish to trigger the system and administer a dose of the drug.  After five days of self-administration, the study authors saw that the fish were exhibiting erratic, even aggressive behavior while triggering or waiting for the drug; the fish even sought out the drug under potentially adverse conditions when the researchers reduced the water level in the area where the drug was released. The fish continued to return to that location, even though they were putting themselves in danger by entering shallow water to receive the drug. 

Based on this research, the study authors concluded that the zebrafish had developed an addiction via the same molecular pathways as other animals, including humans. They also noted that some zebrafish, when treated with the opioid antagonist naloxone, curtailed their drug-seeking behavior during the tests involving hydrocodone self-administration. Using this information, the study authors hope that the zebrafish model can be used in further studies involving the treatment of drug-seeking behavior. Since the model is scalable, it could be applied to any number of drugs, thus reducing the amount of amount of time between research and practical use for those with dependency issues.

"We didn't know if zebrafish would be a relevant model for opioid addiction, much less self-administer the drug," said study senior author Randall T. Peterson, Ph.D., a professor of pharmacology and toxicology at the University of Utah. "What is exciting about this work is that we see many of the hallmarks of addiction in zebrafish. This could be a useful and powerful model."

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Paul Gaita lives in Los Angeles. He has contributed to the Los Angeles Times, Variety, LA Weekly, Amazon.com and The Los Angeles Beat, among many other publications and websites.