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Fighting the opioid crisis... with drug-addled zebrafish

  • Researchers discovered fish react to opioids much the same way addicted humans do.
  • They developed a system for testing new potential therapies.

New methods for treating the rising opioid epidemic in America may be found in the brains and behavior of drug-addicted tropical fish, says a new study.

A team of researchers from the University of Utah Health got a tank full of zebrafish hooked on opioids and found they showed many of the same drug-seeking behaviors humans show, and some of the same symptoms of withdrawal. They also showed similar responses to some of the drugs used to treat addiction.

The trouble with the current therapies for opioid addiction is that they often do not work well — addicts frequently relapse, the scientists said. They say this is a scalable model that could be set up to test other addiction-fighting compounds.

They may seem an unlikely analog for humans, but zebrafish and humans share "key neuronal networks" related to addiction, such as an opioid receptor as well as dopamine and glutamate, that spark the brain's reward system, said the researchers in the paper.

Using a motion sensor and food dispenser, the researchers taught a tank full of fish that they could get a small dose of food every time they swam over a yellow platform.

The team then replaced the food with hydrocodone, a common opioid. The fish did the same thing — they swam over the platform over and over again. Importantly, they had to trigger the sensor to get the dose of the drug — a pump flushed water out of the tank continuously, so it was impossible for them to receive it without swimming over the platform.

They even sought the drug when they had to swim in shallower water, which is typically a more stressful situation zebrafish will avoid if they can. The researchers also confirmed that fish trained only to receive the food, but not the drug, avoided the platform when it was in shallower water.

The fish even sought the drug when the researchers changed the sensor's software to require the fish to swim over the platform multiple times to get a single dose.

When denied the drug, the fish also behaved in ways that have been associated with higher levels of stress and anxiety. For example, anxious fish often explore their environments less, and these fish tended to avoid exploring the outer areas of the tank several hours after being denied the drug.

Fish did seek the drug less when researchers treated them with common drugs used to treat human addicts as well, such as naxolone. The fish triggered the sensor a lot less.

The team also said this model could be used for other substances beyond opioids.

The researchers say their system "could uncover unexpected biological mechanisms" important for drug-seeking behavior and could lead to the identification of potential treatments. "The opportunity of performing this kind of screen is a much-needed addition to the field of addiction research," the team wrote in their paper.