Human beings aren’t the only ones who can become addicted to opioids (learn more about the science of addiction in our special magazine report).
A recent study by researchers at the University of Utah shows that zebrafish, whose neurological structures are similar to humans, can also show signs of addiction to the drugs, providing possibilities for a faster way to test out new therapies that could help people who are addicted.
Randall Peterson, dean of the College of Pharmacy at the University of Utah, says current drug therapies involve other opioids, like methodone or buprenorphine, and they can help a person with one addiction but leave them with a second one when the treatment ends.
"There is still a compelling need for therapies that work in different ways, not just by replacing one opioid with another," he says.
The new zebrafish study is a step toward developing the first therapy that wouldn’t use another opioid in place of the first addiction, Peterson says. Because of how easy it is to test a large variety of drugs that are already approved on large amounts of zebrafish, it could speed up the process of narrowing down promising compounds at a low cost.
The lack of opioid addiction research has hindered scientists’ ability to develop solutions to the growing problem in the U.S. and around the world. There are currently no effective medical treatments for the drug-seeking behavior that humans develop as part of an opioid addiction, according to the paper published in Behavioral Brain Research.
Zebrafish are being used more often to study mental health disorders because of the similarity physiologically and genetically to people, and previous studies have shown that they can develop addictive behavior to a variety of drugs.
"What's new here is that this is a self-administration model where the fish have to perform an action to receive a drug, so that’s fundamentally different in terms of the way the brain responds to the drug," says Peterson. "[This enables] us to measure motivation in drug-seeking in a more complete way."
Gabriel Bosse, lead writer on the study and postdoctoral fellow at Utah's College of Pharmacy, says the new study will help researchers sort through drug compounds to find a few that can be successfully confirmed in additional future studies.
For the study, the researchers used technology that allowed zebrafish in a tank to self-administer opioids. In the video above, the fish swim across the sensor on the yellow-colored platform, which detects their movements.
At first, the motion sensor activated the release of food, which was sent into the tank while a green light flashed. The fish learned that when they want food, they could swim across the platform to get it.
Then the researchers replaced the food with an opioid, still automatically triggered by the movements of the fish. Over the course of a week, their behavior in the tank became increasingly erratic as they frantically and aggressively triggered the release of more of the drug.
In addition, the fish continued to seek out the drug even when researchers gave them a consequence for using it. They made the water in the yellow-platform area shallower by raising the platform up in the tank, which should have deterred the zebrafish because of their natural aversion to shallow water, but the fish continued to return for more doses of the opioid. They also showed signs of stress and anxiety when the drug was taken away from them.
At the end of the study, researchers were able to confirm that the zebrafish who were triggering the release of the drug developed an addiction to it using the same molecular pathways as other animals. The scientists hope further study of this process will provide more insight into how those pathways work, and how they could be treated in people.
"The process of bringing a completely new drug to market can be slow. It can take several years," Peterson says. "One promising alternative is to find a new purpose for an existing drug. This idea … would dramatically reduce the amount of time it would take to get an effective treatment into the hands of doctors and patients."
These fish experiments may help the scientists test such potential drugs.