Zebrafish Willingly Work To Get Opioid Doses: Study


Zebrafish are known to share about 70 percent of their genes with humans and can even exhibit signs of consciousness and emotion, so scientists from the University of Utah set up a small school to explore opioid addiction and its biological and behavioral effects on the fish.

After conditioning the fish to work for food and switching the reward with prescription pain reliever hydrocodone, the researchers observed that the zebrafish exhibited similar behaviors with drug-addicted humans and were even willing to work harder to self-administer doses of the drug.

The researchers noted that the fish also exhibited withdrawal symptoms about two days after the experiment ended, which also happened to be their last exposure to the pain reliever.

The team was actually surprised with the results because, despite their test subject choice, they did not expect to see the fish exhibit drug-seeking behaviors.

"We didn't know if zebrafish would be a relevant model for opioid addiction, much less self-administer the drug," study senior author Randall T. Peterson, Ph.D. said.

Peterson is a professor of pharmacology and toxicology.

Establishing The Trigger And Reward System

Professor Peterson and his colleagues first conditioned the fish to work for their food by using a motion-detection platform inside the tank. The system was an important part of the experiment to confirm drug-seeking behavior because the test subjects were required to work for a dose of the opioid.

When a zebrafish swims over the rigged platform in one corner of the tank, a green bulb lights up, and then a piece of food is dropped near the fish. This was done until the fish understood that it will get a treat whenever it swims over the rigged platform, as opposed to the identical but inactive platform on the other side of the tank.

After the trigger and reward system were established and the fish behavior was conditioned, the researchers switched the food with doses of hydrocodone. There was also a continuous flow of water in the tank so the drug would be flushed away, forcing the fish to swim back to the platform for another dose if they want.

Researchers noted that the fish showed signs of addiction after one week of exposure to the drug.

Drug-Addicted Fish

Over the course of five days of triggered exposure, the zebrafish actually self-administered hydrocodone more often throughout the 50-minute sessions of the experiment.

The researchers observed that the zebrafish tended to self-administer more drugs in two other situations: first was when the fish became stressed when the water in the tank became progressively shallower, and second was when the team lowered the dosage of the drug. In the latter situation, the fish self-administered more often to match the original dose it received.

"This was important, because we forced the fish to do more work to receive [the original dose of] the drug, and they were more than willing to do more work," Peterson said.

Withdrawal And Treatment

As already mentioned, the zebrafish also exhibited withdrawal symptoms once the source of their addiction was removed from the tank.

The team treated the addicted fish with naloxone to block out their m-opioid receptor and glutamate- or dopamine-blockers, but it only helped to reduce their addictive behavior.

The team is now looking at using their addicted fish model to find other ways to stop the drug-seeking behavior and possibly apply it to humans.

"This could be a useful and powerful model," Peterson expressed.

Watch the drug-addicted zebrafish work for their fix below.

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