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Study suggests opioid-addicted zebrafish could be key to finding new human treatment

In this Monday, Aug. 14, 2017 photo zebrafish swim in a container at a laboratory at Boston Children's Hospital, in Boston. Researchers at WSU are studying jaw protrusion, an ability shared by zebrafish and other species, for insight into human skull development. (Steven Senne / AP)
By Travis M. Andrews Washington Post

As the opioid epidemic sweeps through America, scientists are scrambling to understand its addictive power in hopes of developing new treatment methods.

In the process, they discovered that zebrafish can become opioid addicts. Researchers at the University of Utah hope their study of the addicted fish could be helpful in creating new treatments for humans.

They outlined their findings in a paper recently published in the journal Behavioral Brain Research.

The goal of the research is to find a new method of treating opioid addiction that doesn’t require other opioids. At present treatment for heroin addiction, for example, involves substituting another drug, such as methadone, for the heroin, in hopes that addicts’ usage will eventually taper off.

“There is still a compelling need for therapies that work in different ways, not just by replacing one opioid with another,” Randall Peterson, dean of the College of Pharmacy at the University of Utah, told National Geographic.

Zebrafish are a freshwater tropical fish that grow to about 2 inches in length and have a black and white pattern, much like zebras. Researchers observed their addictive behavior in an environment where the fish could self-administer opioids.

First, they set up a fish tank containing two platforms on opposite sides, one white and one yellow. The yellow platform contained a sensor. When the fish swam over the sensor, it released food while a green light flashed. Nothing happened when they swam over the white platform.

Then, once the zebrafish learned how the sensor worked, researchers replaced the food with hydrocodone, an opioid commonly known as Vicodin. With each pass, the drug was released into the water and ingested by the fish. The water was continuously flushed out of the tank and replenished, so the fish had to repeatedly trigger the sensor to receive more of the drug.

The fish quickly reacted to the drug, flocking to the yellow opioid-dispensing platform at an astounding rate. They were placed in the tank for 50 minutes each day for five days. During each session, some of the fish visited the opioid platform nearly 2,000 times.

When the drug was removed, they visited it about 200 times on average and showed signs of agitation and anxiety, the study said. And when the researchers raised the opioid platform so the water over it was shallow – a condition zebrafish naturally go to lengths to avoid – the fish continuously swam up to the platform for more hydrocodone.

“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,” Peterson told National Geographic. “This enables us to measure motivation in drug-seeking in a more complete way.”

The study is important, because not only do zebrafish share 70 percent of the same genes with humans, as Futurism reported, they also share a similar neurological makeup – an 5-opioid receptor and two neurotransmitters – to humans, meaning they react to addiction in the same way.

“Drugs of abuse target the pathways of the pleasure centers very effectively,” Gabriel Bossi, an author on the study, told Medical Xpress. “These pathways are conserved in zebrafish, and the fish can experience some of the same signs of addiction and withdrawal as people.”

An estimated 2.6 million people in the United States are addicted to opioids, as the Post noted. In 2015 alone, more than 33,000 Americans died by overdosing on various opioids, be they prescription pain relievers or heroin, according to the American Society of Addition Medicine.

President Donald Trump declared the opioid crisis a national emergency in early August.

“The opioid crisis is an emergency, and I’m saying officially right now it is an emergency,” he said. “It’s a national emergency. We’re going to spend a lot of time, a lot of effort and a lot of money on the opioid crisis.”

Bringing new treatment methods to market is a slow process. Zebrafish could prove advantageous as test subjects and help accelerate the process because they are prolific breeders, the Utah researchers said. One female fish can produce 200 eggs each day, according to the Verge.

Not only could researchers study addiction on thousands of fish, they could also trace potential genetic mutations stemming from addiction, the researchers said.